Data for the Products of Quinazolines by Cobalt(III)-Catalyzed C─H/N─O

Characterization Data

4-Ethoxy-2-phenylquinazoline (163aa): The general procedure C was followed using ethyl benzimidate (161a) (37.3 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 30/1) yielded 163aa (60 mg, 96%) as a white solid.

The analytical data were in accordance with those reported in the literature.^[199]

4-Methoxy-2-phenylquinazoline (163ba): The general procedure C was followed using methyl benzimidate (161b) (33.8 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163ba (43.0 mg, 73%) as a white solid.

M. p. = 49─50 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.63─8.60 (m, 2H), 8.16 (ddd, J = 8.2, 1.5, 0.7 Hz, 1H), 8.00 (ddd, J = 8.4, 1.2, 0.7 Hz, 1H), 7.81 (ddd, J = 8.5, 7.0, 1.5 Hz, 1H), 7.55─7.48 (m, 4H), 4.29 (s, 3H). ¹³C NMR (100 MHz, CDCl3) δ = 167.2 (Cq), 160.2 (Cq), 152.0 (Cq), 138.3 (Cq), 133.6 (CH), 130.6

Experimental Section

(CH), 128.6 (CH), 128.5 (CH), 128.1 (CH), 126.5 (CH), 123.6 (CH), 115.4 (Cq), 54.2 (CH3). IR (ATR) ν = 3058, 1620, 1557, 1501, 1444, 1375, 1103, 911, 759, 672 cm^-1. MS (ESI) m/z (relative intensity): 237 (100) [M+H]⁺. HR-MS (ESI) m/z calcd for C15H13N2O [M+H]⁺: 237.1022, found: 237.1026.

The analytical data were in accordance with those reported in the literature.^[199]

4-Ethoxy-7-methyl-2-phenylquinazoline (163ca): The general procedure C was followed using ethyl 4-methylbenzimidate (161c) (40.8 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163ca (60.0 mg, 91%) as a white solid.

The analytical data were in accordance with those reported in the literature.^[199]

4-Ethoxy-7-methoxy-2-phenylquinazoline (163da): The general procedure C was followed using ethyl 4-methoxybenzimidate (161d) (44.8 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc:

40/1) yielded 163da (62.2 mg, 89%) as a white solid.

M. p. = 131─132 ˚C. ¹H NMR (400 MHz, CDCl3) δ = 8.55 (dd, J = 7.8, 1.9 Hz, 2H), 8.02 (d, J = 9.3 Hz, 1H), 7.63─7.41 (m, 3H), 7.29 (d, J = 2.5 Hz, 1H), 7.08 (dd, J = 9.0, 2.5 Hz, 1H), 4.72 (q, J = 7.1 Hz, 2H),

Experimental Section

The analytical data were in accordance with those reported in the literature.^[199]

4-Ethoxy-2-phenyl-7-(trifluoromethyl)quinazoline (163ea): The general procedure C was followed using ethyl 4-(trifluoromethyl)benzimidate (161e) (54.3 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163ea (66.9 mg, 84%) as a white solid.

M. p. = 101─103 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.56 (dd, J = 6.5, 3.3 Hz, 2H), 8.23 (d, J = 7.9 Hz,

4-Ethoxy-7-fluoro-2-phenylquinazoline (163fa): The general procedure C was followed using ethyl 4-fluorobenzimidate (161f) (41.8 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163fa (66.9 mg, 98%) as a white solid.

Experimental Section 2975, 1626, 1562, 1416, 1340, 1156, 1018, 861, 770, 676 cm^-1. MS (ESI) m/z (relative intensity): 241 (30), 269 (100) [M+H]⁺, 291 (100) [M+Na]⁺. HR-MS (ESI) m/z calcd for C16H14N2OF [M+H]⁺: 269.1085, found: 269.1086.

7-Chloro-4-ethoxy-2-phenylquinazoline (163ga): The general procedure C was followed using ethyl 4-chlorobenzimidate (161g) (45.9 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163ga (68.0 mg, 96%) as a white solid.

The analytical data were in accordance with those reported in the literature.^[199]

Experimental Section

166

1-(4-Ethoxy-2-phenylquinazolin-7-yl)ethanone (163ha): The general procedure C was followed using ethyl 4-acetylbenzimidate (161h) (47.8 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163ha (53.4 mg, 73%) as a pale yellow solid.

Methyl 4-methoxy-2-phenylquinazoline-7-carboxylate (163ia): The general procedure C was followed using methyl 4-[imino(methoxy)methyl]benzoate (161i) (48.3 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 20/1) yielded 163ia (48.0 mg, 72%) as a white solid.

M. p. = 124─125 ˚C. ¹H NMR (400 MHz, CDCl3) δ = 8.62 (d, J = 2.1 Hz, 1H), 8.60─8.54 (m, 2H), 8.14 (dd, J =8.5, 0.7 Hz, 1H), 8.07─8.03 (m, 1H), 7.55─7.45 (m, 3H), 4.26 (s, 3H), 3.97 (s, 3H). ¹³C NMR (100 MHz, CDCl3) δ = 166.9 (Cq), 166.3 (Cq), 160.7 (Cq), 151.4 (Cq), 137.7 (Cq), 134.5 (Cq), 130.7 (CH), 130.1 (CH), 128.5 (CH), 128.4 (CH), 125.9 (CH), 123.7 (CH), 117.6 (Cq), 54.3 (CH3), 52.5 (CH3). IR (ATR) ν = 2945, 1718, 1556, 148.99, 1373, 1267, 909, 753, 713 cm^-1. MS (ESI) m/z (relative intensity): 295 (100) [M+H]⁺, 317 (95) [M+Na]⁺. HR-MS (ESI) m/z calcd for C17H15N2O3 [M+H]⁺: 295.1077, found:

295.1080.

Experimental Section

4-Ethoxy-7-nitro-2-phenylquinazoline (163ja): The general procedure C was followed using ethyl 4-nitrobenzimidate (161j) (48.9 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163ja (42.0 mg, 57%) as a white solid.

4-Ethoxy-6-methyl-2-phenylquinazoline (163ka): The general procedure C was followed using ethyl 3-methylbenzimidate (161k) (41.0 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163ka (60.0 mg, 91%) as a white solid.

The analytical data were in accordance with those reported in the literature.^[199]

Experimental Section

168

4-Ethoxy-2-phenyl-6-(trifluoromethyl)quinazoline (163la): The general procedure C was followed using ethyl 3-(trifluoromethyl)benzimidate (161l) (54.3 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163la (46.0 mg, 58%) as a white solid.

M. p. = 129─130 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.62─8.52 (m, 2H), 8.45 (t, J = 0.9 Hz, 1H), 8.05 (d,

6-Chloro-4-ethoxy-2-phenylquinazoline (163ma): The general procedure C was followed using ethyl 3-chlorobenzimidate (161m) (46 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163ma (62.3 mg, 88%) as a white solid.

Experimental Section

4-Ethoxy-2-phenylthieno[2,3-d]pyrimidine (163na): The general procedure C was followed using ethyl thiophene-3-carbimidate (161n) (39 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 15/1) yielded 163na (38.0 mg, 60%) as a white solid.

2-Benzyl-4-ethoxyquinazoline (163ab): The general procedure C was followed using ethyl benzimidate (161a) (37.3 mg, 0.25 mmol) and 5-benzyloxazol-2(5H)-one (162b) (52.6 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 15/1) yielded 163ab (56.9 mg, 88%) as a yellow oil.

The analytical data were in accordance with those reported in the literature.^[199]

Experimental Section

170

4-Ethoxy-2-phenethylquinazoline (163ac): The general procedure C was followed using ethyl benzimidate (161c) (37.3 mg, 0.25 mmol) and 5-phenethyloxazol-2(5H)-one (162a) (56.8 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 20/1) yielded 163ac (56.9 mg, 82%) as a colorless oil. m/z (relative intensity): 279 (100) [M+H]⁺. IR (ATR) ν = 2979, 1620, 1572, 1496, 1419, 1322, 1103, 769, 683 cm^-1. HR-MS (ESI) m/z calcd for C18H18N2O [M+H]⁺: 279.1492, found: 279.1497.

4-Ethoxy-2-tridecylquinazoline (163ad): The general procedure C was followed using ethyl benzimidate (161a) (37.3 mg, 0.25 mmol) and 5-tridecyloxazol-2(5H)-one (162d) (80.8 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 30/1) yielded 163ad (54.0 mg, 61%) as a colorless oil.

Experimental Section

4-Ethoxy-2-(thiophen-3-yl)quinazoline (163ae): The general procedure C was followed using ethyl benzimidate (161a) (37.3 mg, 0.25 mmol) and 5-(thiophen-3-yl)oxazol-2(5H)-one (162e) (50.7 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163ae (58.1 mg, 91%) as a colorless oil.

4-Ethoxy-2-(4-methoxyphenyl)quinazoline (163af): The general procedure C was followed using ethyl benzimidate (161a) (37.3 mg, 0.25 mmol) and 5-(4-methoxyphenyl)oxazol-2(5H)-one (162f) (57.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 20/1) yielded 163af (46.9 mg, 68%) as a white solid. ν = 3047, 1603, 1574, 1497, 1328, 1249, 1151, 765, 680, 542 cm^-1. MS (ESI) m/z (relative intensity):

281 (100) [M+H]⁺. HRMS (ESI) m/z calcd for C17H17N2O2 [M+H]⁺: 281.1290 found 281.1285.

Experimental Section

172

The analytical data were in accordance with those reported in the literature.^[200]

4-Ethoxy-2-(m-tolyl)quinazoline (163ag): The general procedure C was followed using ethyl benzimidate (161a) (37.3 mg, 0.25 mmol) and 5-(m-tolyl)oxazol-2(5H)-one (162g) (53.2 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163ag (56.9 mg, 86%) as a white solid.

2-(3-Chlorophenyl)-4-ethoxyquinazoline (163ah): The general procedure C was followed using ethyl benzimidate (161a) (37.3 mg, 0.25 mmol) and 5-(3-chlorophenyl)oxazol-2(5H)-one (162h) (59.3 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1) yielded 163ah (43.4 mg, 61%) as a white solid.

M. p. = 85─87 ˚C. ¹H NMR (400 MHz, CDCl3) δ = 8.54 (td, J = 1.7, 0.7 Hz, 1H), 8.48.9─8.38 (m, 1H), 8.15 (ddd, J = 8.2, 1.5, 0.7 Hz, 1H), 7.95 (ddd, J = 8.4, 1.1, 0.7 Hz, 1H), 7.79 (ddd, J = 8.5, 7.0, 1.5 Hz, 1H), 7.50 (ddd, J = 8.2, 7.0, 1.2 Hz, 1H), 7.45─7.36 (m, 2H), 4.74 (q, J = 7.1 Hz, 2H), 1.56 (t, J = 7.1 Hz, 3H). ¹³C NMR (100 MHz, CDCl3) δ = 166.8 (Cq), 158.6 (Cq), 151.7 (Cq), 140.1 (Cq), 134.5 (Cq), 133.5

Experimental Section

(CH), 130.3 (CH), 129.6 (CH), 128.5 (CH), 127.9 (CH), 126.6 (CH), 126.5 (CH), 123.5 (CH), 115.5 (Cq), 63.0 (CH2), 14.4 (CH3). IR (ATR) ν = 2975, 1620, 1575, 1499, 1418, 1325, 1171, 1015, 764, 672 cm^-1. MS (ESI) m/z (relative intensity): 285 (100) [M+H]⁺, 307 (30) [M+Na]⁺. HR-MS (ESI) m/z calcd for C16H14N2OCl [M+H]⁺: 285.0789, found: 285.0788.

The analytical data were in accordance with those reported in the literature.^[199]

4-Ethoxy-2-(3-fluorophenyl)quinazoline (163ai): The general procedure C was followed using ethyl benzimidate (161a) (37.3 mg, 0.25 mmol) and 3-(3-fluorophenyl)-1,4,2-dioxazol-5H-one (162i) (54.3 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 40/1)

2-(4-Chlorophenyl)-4-ethoxyquinazoline (163aj): The general procedure C was followed using ethyl benzimidate (161a) (37.3 mg, 0.25 mmol) and 5-(4-chlorophenyl)oxazol-2(5H)-one (162j) (59.3 mg,

Experimental Section

174

0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 30/1) yielded 163aj (66.0 mg, 93%) as a white solid.

The analytical data were in accordance with those reported in the literature.^[199]

4-Ethoxy-2-(4-nitrophenyl)quinazoline (163ak): The general procedure C was followed using ethyl benzimidate (161a) (37.3 mg, 0.25 mmol) and 5-(4-nitrophenyl)oxazol-2(5H)-one (162k) (62.4 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 20/1) yielded 163ak (44.8 mg, 60%) as a pale yellow solid.

Experimental Section

4-Ethoxy-2-phenyl-7-(1H-pyrazol-1-yl)quinazoline (163ka): The general procedure C was followed using ethyl 4-(1H-pyrazol-1-yl)benzimidate (161k) (53.8 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 25/1) yielded 163ka (55.4 mg, 70%) as a white solid.

M. p. = 129─130 ˚C. ¹H NMR (400 MHz, CDCl3) δ = 8.62─8.50 (m, 2H), 8.21 (dd, J = 8.9, 0.5 Hz, 1H),

4-Ethoxy-2-(4-methoxyphenyl)-7-(1H-pyrazol-1-yl)quinazoline (163kf): The general procedure C was followed using ethyl 4-(1H-pyrazol-1-yl)benzimidate (161k) (53.8 mg, 0.25 mmol) and 3-(4-methoxyphenyl)-1,4,2-dioxazol-5-one (162f) (58.0 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 6/1) yielded 163kf (51.0 mg, 59%) as a white solid.

M. p. = 138─140 ˚C. ¹H NMR (400 MHz, CDCl3) δ = 8.51 (d, J = 9.0 Hz, 2H), 8.19 (dd, J = 8.9, 0.6 Hz,

Experimental Section

176

1422, 1331, 1159, 1018, 749 cm^-1. MS (ESI) m/z (relative intensity): 236 (20), 347 (100) [M+H]⁺, 369 (20) [M+Na]⁺, 715 (10) [2M+Na]⁺. HR-MS (ESI) m/z calcd for C20H19N4O2 [M+H]⁺: 347.1503, found:

347.1504.

4-Ethoxy-7-(1H-pyrazol-1-yl)-2-(m-tolyl)quinazoline (163kg): The general procedure C was followed using ethyl 4-(1H-pyrazol-1-yl)benzimidate (161k) (53.8 mg, 0.25 mmol) and 3-(m-tolyl)-1,4,2-dioxazol-5-one (162g) (53.2 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 20/1) yielded 163kg (51.8 mg, 63%) as a white solid.

M. p. = 149─151 ˚C. ¹H NMR (400 MHz, CDCl3) δ = 8.38─8.33 (m, 2H), 8.23 (dd, J = 8.9, 0.6 Hz, 1H),

4-Ethoxy-2-(3-fluorophenyl)-7-(1H-pyrazol-1-yl)quinazoline (163ki): The general procedure C was followed using ethyl 4-(1H-pyrazol-1-yl)benzimidate (161k) (53.8 mg, 0.25 mmol) and 3-(3-fluorophenyl)-1,4,2-dioxazol-5-one (162i) (54.4 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 15/1) yielded 163ki (49.1 mg, 59%) as a white solid.

M. p. = 154─155 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.39 (dt, J = 7.8, 1.1 Hz, 1H), 8.34─8.23 (m, 2H),

Experimental Section followed using ethyl 4-(1H-pyrazol-1-yl)benzimidate (161k) (53.8 mg, 0.25 mmol) and 3-(3-chlorophenyl)-1,4,2-dioxazol-5-one (162h) (59.3 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 20/1) yielded 163kh (56.3 mg, 64%) as a white solid.

M. p. = 168─170 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.56 (d, J = 1.8 Hz, 1H), 8.46 (dt, J = 6.8, 1.8 Hz,

Experimental Section

178

4-Ethoxy-2-phenethyl-7-(1H-pyrazol-1-yl)quinazoline (163kc): The general procedure C was followed using ethyl 4-(1H-pyrazol-1-yl)benzimidate (161k) (53.8 mg, 0.25 mmol) and 3-phenethyl-1,4,2-dioxazol-5-one (162c) (57.4 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 6/1) yielded 163kc (47.2 mg, 55%) as a white solid.

M. p. = 92─93 ˚C. ¹H NMR (400 MHz, CDCl3) δ = 8.20 (dd, J = 8.9, 0.6 Hz, 1H), 8.09 (dd, J = 2.6, 0.6

4-Ethoxy-7-(1H-pyrazol-1-yl)-2-(thiophen-3-yl)quinazoline (163ke): The general procedure C was followed using ethyl 4-(1H-pyrazol-1-yl)benzimidate (161k) (53.8 mg, 0.25 mmol) and 3-(thiophen-3-yl)-1,4,2-dioxazol-5-one (162e) (51.8 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 6/1) yielded 163ke (65.0 mg, 81%) as a white solid.

M. p. = 167─169 ˚C. ¹H NMR (400 MHz, CDCl3) δ = 8.20─8.11 (m, 1H), 8.09 (d, J = 2.6 Hz, 1H), 8.04 (dd, J = 3.7, 1.2 Hz, 1H), 8.02─7.96 (m, 2H), 7.77 (d, J = 1.4 Hz, 1H), 7.46 (dd, J = 5.0, 1.2 Hz, 1H), 7.13 (dd, J = 5.0, 3.7 Hz, 1H), 6.50 (dd, J = 2.6, 1.8 Hz, 1H), 4.68 (q, J = 7.1 Hz, 2H), 1.53 (t, J = 7.1 Hz, 3H).

13C NMR (100 MHz, CDCl3) δ = 166.2 (Cq), 157.8 (Cq), 152.6 (Cq), 144.0 (Cq), 143.7 (Cq), 141.9 (CH), 129.8 (CH), 129.1 (CH), 128.0 (CH), 127.0 (CH), 125.3 (CH), 118.0 (CH), 114.5 (CH), 113.1 (Cq), 108.6

Experimental Section

(CH), 63.1 (CH2), 14.3 (CH3). IR (ATR) ν = 3115, 2979, 1624, 1565, 1414, 1330, 1167, 875, 779, 704 cm^-1. MS (ESI) m/z (relative intensity): 323 (100) [M+H]⁺, 345 (55) [M+Na]⁺, 667 (45) [2M+Na]⁺. HR-MS (ESI) m/z calcd for C17H15N4OS [M+H]⁺: 323.0961, found: 323.0960.

4-Ethoxy-2-phenyl-6-(1H-pyrazol-1-yl)quinazoline (163la): The general procedure C was followed using ethyl 3-(1H-pyrazol-1-yl)benzimidate (161l) (53.8 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 10/1 to 6/1) yielded 163la (48.9 mg, 62%) as a white solid.

M. p. = 130─131 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.61─8.50 (m, 2H), 8.35 (d, J = 2.5 Hz, 1H), 8.19 (dd, J = 9.1, 2.6 Hz, 1H), 8.07─7.95 (m, 2H), 7.77 (d, J = 1.7 Hz, 1H), 7.53─7.44 (m, 3H), 6.51 (dd, J = 2.5, 1.8 Hz, 1H), 4.76 (d, J = 7.1 Hz, 2H), 1.56 (t, J = 7.1 Hz, 3H). ¹³C NMR (75 MHz, CDCl3) δ = 166.5 (Cq), 159.9 (Cq), 150.2 (Cq), 141.6 (CH), 137.9 (Cq), 137.7 (Cq), 130.5 (CH), 129.5 (CH), 128.7 (CH), 128.3 (CH), 126.9 (CH), 125.4 (CH), 115.6 (Cq), 112.0 (CH), 108.1 (CH), 63.1 (CH2), 14.4 (CH3). IR (ATR) ν = 2983, 1579, 1507, 1391, 1312, 1019, 774, 701, 560 cm^-1. MS (ESI) m/z (relative intensity):

345 (100) [M+H]⁺, 367 (20) [M+Na]⁺. HR-MS (ESI) m/z calcd for C20H17N4O2 [M+H]⁺: 345.1346, found: 345.1347.

2-(4-Bromophenyl)-4-ethoxy-7-(5-methyl-1H-pyrazol-1-yl)quinazoline (163ml): The general procedure C was followed using ethyl 4-(5-methyl-1H-pyrazol-1-yl)benzimidate (161m) (57.3 mg, 0.25 mmol) and 3-(4-bromophenyl)-1,4,2-dioxazol-5-one (162l) (72.6 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 15/1) yielded 163ml (63.1 mg, 64%) as a white solid.

M. p. = 184─186 ˚C. ¹H NMR (400 MHz, CDCl3) δ = 8.39 (d, J = 8.6 Hz, 2H), 8.15 (d, J = 9.7 Hz, 1H), 8.05─7.94 (m, 3H), 7.59 (d, J = 8.5 Hz, 2H), 6.30 (d, J = 2.5 Hz, 1H), 4.70 (q, J = 7.1 Hz, 2H), 2.39 (s,

Experimental Section procedure C was followed using ethyl 4-(5-methyl-1H-pyrazol-1-yl)benzimidate (161m) (57.3 mg, 0.25 mmol) and 5-(4-nitrophenyl)oxazol-2(5H)-one (162k) (62.4 mg, 0.30 mmol). Purification by column chromatography on silica gel (n-hexane/EtOAc: 10/1 to 4/1) yielded 163mk (54.4 mg, 58%) as a yellow solid.

4-Ethoxy-2-phenyl-7-(pyrimidin-2-yl)quinazoline (163na): The general procedure C was followed using ethyl 4-(pyrimidin-2-yl)benzimidate (161n) (56.9 mg, 0.25 mmol) and

Experimental Section

5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 5/1) yielded 163na (60 mg, 73%) as a white solid.

M. p. = 145─146 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 9.08 (d, J = 1.1 Hz, 1H), 8.86 (d, J = 4.8 Hz, 2H), 8.67─8.57 (m, 2H), 8.54 (dd, J = 8.6, 1.6 Hz, 1H), 8.23 (dd, J = 8.6, 0.6 Hz, 1H), 7.70─7.41 (m, 3H), 7.24 (t, J = 4.8 Hz, 1H), 4.77 (q, J = 7.1 Hz, 2H), 1.57 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl3) δ = 166.5 (Cq), 163.8 (Cq), 160.2 (Cq), 157.2 (CH), 152.1 (Cq), 142.1 (Cq), 138.1 (Cq), 130.3 (CH), 128.4 (CH), 128.3 (CH), 128.0 (CH), 125.4 (CH), 123.7 (CH), 119.7 (CH), 116.5 (Cq), 62.9 (CH2), 14.5 (CH3). IR (ATR) ν = 2974, 1623, 1562, 1431, 1324, 1163, 1025, 756, 708 cm^-1. MS (ESI) m/z (relative intensity): 329 (100) [M+H]⁺, 351 (40) [M+Na]⁺. HR-MS (ESI) m/z calcd for C20H17N4O [M+H]⁺: 329.1397, found:

329.1397.

2-(4-Chlorophenyl)-4-ethoxy-7-(pyrimidin-2-yl)quinazoline (163nj): The general procedure C was followed using ethyl 4-(pyrimidin-2-yl)benzimidate (161n) (56.8 mg, 0.25 mmol) and 3-(4-chlorophenyl)-1,4,2-dioxazol-5-one (162j) (59.3 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 6/1) yielded 163nj (64.4 mg, 71%) as a yellow solid.

M. p. = 198─190 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 9.02 (d, J = 1.2 Hz, 1H), 8.85 (d, J = 4.8 Hz, 2H),

Experimental Section

182

2-(4-Bromophenyl)-4-ethoxy-7-(pyrimidin-2-yl)quinazoline (163nl): The general procedure C was followed using ethyl 4-(pyrimidin-2-yl)benzimidate (161n) (56.8 mg, 0.25 mmol) and 3-(4-bromophenyl)-1,4,2-dioxazol-5-one (162l) (72.6 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 5/1) yielded 163nl (87.0 mg, 85%) as a white solid.

M. p. = 191─193 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 9.03 (d, J = 1.3 Hz, 1H), 8.85 (d, J = 4.8 Hz, 2H), 8.53 (dd, J = 8.6, 1.7 Hz, 1H), 8.43 (d, J = 8.6 Hz, 2H), 8.20 (d, J = 8.6 Hz, 1H), 7.59 (d, J = 8.6 Hz, 2H), 7.24 (t, J = 4.8 Hz, 1H), 4.72 (q, J = 7.1 Hz, 2H), 1.55 (t, J = 7.1 Hz, 3H). ¹³C NMR (75 MHz, CDCl3) δ = 166.7 (Cq), 163.7 (Cq), 159.3 (Cq), 157.4 (CH), 152.0 (Cq), 142.3 (Cq), 137.1 (Cq), 131.5 (CH), 130.0 (CH), 128.0 (CH), 125.7 (CH), 125.1 (Cq), 123.7 (CH), 119.8 (CH), 116.5 (Cq), 63.0 (CH2), 14.4 (CH3). IR (ATR) ν = 2976, 1625, 1560, 1414, 1325, 1160, 1011, 837, 785, 738 cm^-1. MS (ESI) m/z (relative intensity):

301 (10), 360 (10), 407 (100) [M+H]⁺, 409 (100). HR-MS (ESI) m/z calcd for C20H16N4OBr [M+H]⁺: 407.0502, found: 407.0499.

4-Ethoxy-2-phenyl-7-(pyrazin-2-yloxy)quinazoline (163oa): The general procedure C was followed using ethyl 4-(pyrazin-2-yloxy)benzimidate (161o) (60.8 mg, 0.25 mmol) and 5-phenyloxazol-2(5H)-one (162a) (48.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 10/1) yielded 163oa (76.9 mg, 89%) as a white solid.

M. p. = 129─130 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.60─8.45 (m, 3H), 8.33 (d, J = 2.7 Hz, 1H), 8.20 (dd, J = 8.9, 0.4 Hz, 1H), 8.13 (dd, J = 2.7, 1.4 Hz, 1H), 7.70 (dd, J = 2.3, 0.4 Hz, 1H), 7.53─7.42 (m, 3H), 7.29 (dd, J = 8.9, 2.3 Hz, 1H), 4.76 (q, J = 7.1 Hz, 2H), 1.55 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl3) δ = 166.3 (Cq), 160.8 (Cq), 159.3 (Cq), 157.2 (Cq), 153.3 (Cq), 141.1 (CH), 139.3 (CH), 137.9 (Cq), 136.3 (CH), 130.5 (CH), 128.4 (CH), 128.3 (CH), 125.4 (CH), 120.6 (CH), 117.6 (CH), 112.7 (Cq), 62.9

Experimental Section

(CH2), 14.5 (CH3). IR (ATR) ν = 2975, 1623, 1579, 1405, 1343, 1285, 1150, 1107, 848, 706 cm^-1. MS (ESI) m/z (relative intensity): 317 (100) [M+H]⁺, 339 (40) [M+Na]⁺. HR-MS (ESI) m/z calcd for C19H17N4O [M+H]⁺: 317.1397, found: 317.1397.

4-Ethoxy-7-(pyrazin-2-yloxy)-2-(p-tolyl)quinazoline (163om): The general procedure C was followed using ethyl 4-(pyridin-2-yloxy)benzimidate (161o) (60.8 mg, 0.25 mmol) and 3-(p-tolyl)-1,4,2-dioxazol-5-one (162m) (53.1 mg, 0.30 mmol). Purification by column chromatography on silica gel (n-hexane/EtOAc: 10/1) yielded 163om (67.2 mg, 75%) as a white solid.

M. p. = 151─153 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.54 (d, J = 1.4 Hz, 1H), 8.45 (d, J = 8.2 Hz, 2H), 8.35 (d, J = 2.7 Hz, 1H), 8.22 (d, J = 8.9 Hz, 1H), 8.16 (dd, J = 2.7, 1.4 Hz, 1H), 7.70 (d, J = 2.3 Hz, 1H), 7.35─7.24 (m, 3H), (dd, J = 8.8, 2.3 Hz, 1H), 4.78 (q, J = 7.1 Hz, 2H), 2.43 (s, 3H), 1.57 (t, J = 7.1 Hz, 3H). ¹³C NMR (75 MHz, CDCl3) δ = 166.6 (Cq), 161.3 (Cq), 159.7 (Cq), 157.5 (Cq), 153.7 (Cq), 141.4 (CH), 141.0 (Cq), 139.6 (CH), 136.5 (CH), 135.5 (Cq), 129.3 (CH), 128.7 (CH), 125.7 (CH), 120.6 (CH), 117.8 (CH), 112.9 (Cq), 63.0 (CH2), 21.7 (CH3), 14.6 (CH3). IR (ATR) ν = 2981, 1623, 1575, 1558, 1419, 1399, 1381, 1275, 1177, 1160 cm^-1. MS (ESI) m/z (relative intensity): 359 (100) [M+H]⁺, 376 (4) [M+Na]⁺. HR-MS (ESI) m/z calcd for C21H19N4O2 [M+H]⁺: 359.1508, found: 359.1503.

4-Ethoxy-7-(pyrazin-2-yloxy)-2-(thiophen-3-yl)quinazoline (163og): The general procedure C was followed using ethyl 4-(pyrazin-2-yloxy)benzimidate (161o) (60.8 mg, 0.25 mmol) and 5-(m-tolyl)oxazol-2(5H)-one (162g) (53.1 mg, 0.30 mmol). Purification by column chromatography on silica gel (n-hexane/EtOAc: 4/1) yielded 163og (75.3 mg, 84%) as a white solid.

Experimental Section

2-(4-Chlorophenyl)-4-ethoxy-7-(pyrazin-2-yloxy)quinazoline (163oj): The general procedure C was followed using ethyl 4-(pyrazin-2-yloxy)benzimidate (161o) (60.8 mg, 0.25 mmol) and 5-(4-chlorophenyl)oxazol-2(5H)-one (162j) (59.3 mg, 0.30 mmol). Purification by column chromatography on silica gel (n-hexane/EtOAc: 10/1) yielded 163oj (82.3 mg, 87%) as a white solid.

M. p. = 167─169 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.54 (dd, J = 1.4, 0.5 Hz, 1H), 8.53─8.47 (m, 2H),

Experimental Section

4-Ethoxy-2-(4-nitrophenyl)-7-(pyrazin-2-yloxy)quinazoline (163ok): The general procedure C was followed using ethyl 4-(pyridin-2-yloxy)benzimidate (161o) (60.8 mg, 0.25 mmol) and 5-(4-nitrophenyl)oxazol-2(5H)-one (162k) (62.4 mg, 0.30 mmol). Purification by column chromatography on silica gel (n-hexane/EtOAc: 10/1 to 4/1) yielded 163ok (69.1 mg, 71%) as a 1401, 1345, 1280, 1167, 1082 cm^-1. MS (ESI) m/z (relative intensity): 412 (100) [M+Na]⁺. HR-MS (ESI) m/z calcd for C20H15N5O4Na [M+Na]⁺: 412.1022, found: 412.1016.

2-Benzyl-4-ethoxy-7-(pyrazin-2-yloxy)quinazoline (163ob): The general procedure C was followed using ethyl 4-(pyrazin-2-yloxy)benzimidate (161o) (60.8 mg, 0.25 mmol) and 5-benzyloxazol-2(5H)-one (162b) (53.1 mg, 0.30 mmol). Purification by column chromatography on silica gel (n-hexane/EtOAc: 3/2) yielded 163ob (69.9 mg, 78%) as a white solid.

M. p. = 122─124 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.54 (d, J = 1.4 Hz, 1H), 8.36 (d, J = 2.7 Hz, 1H), 8.18 (d, J = 8.9 Hz, 1H), 8.16 (dd, J = 2.8, 1.4 Hz, 1H), 7.64 (dd, J = 2.4, 0.5 Hz, 1H), 7.48─7.45 (m, 2H), 7.33─7.28 (m, 3H), 7.25─7.19 (m, 1H), 4.62 (q, J = 7.1 Hz, 2H), 4.25 (s, 2H), 1.46 (t, J = 7.1 Hz, 3H). ¹³C NMR (75 MHz, CDCl3) δ = 166.6 (Cq), 166.5 (Cq), 159.5 (Cq), 157.4 (Cq), 153.2 (Cq), 141.4 (CH), 139.6

Experimental Section

4-Ethoxy-2-phenethyl-7-(pyrazin-2-yloxy)quinazoline (163oc): The general procedure C was followed using ethyl 4-(pyrazin-2-yloxy)benzimidate (161o) (60.6 mg, 0.25 mmol) and 5-phenethyloxazol-2(5H)-one (162c) (57.3 mg, 0.30 mmol). Purification by column chromatography on silica gel (n-hexane/EtOAc: 4/1) yielded 163oc (81.0 mg, 87%) as a white solid.

M. p. = 94─96 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.52 (d, J = 1.4 Hz, 1H), 8.35 (d, J = 2.6 Hz, 1H), 8.20

4-Ethoxy-7-(pyrazin-2-yloxy)-2-(thiophen-3-yl)quinazoline (163oe): The general procedure C was followed using ethyl 4-(pyrazin-2-yloxy)benzimidate (161o) (60.8 mg, 0.25 mmol) and 5-(thiophen-3-yl)oxazol-2(5H)-one (162e) (50.7 mg, 0.30 mmol). Purification by column chromatography on silica gel (n-hexane/EtOAc: 4/1) yielded 163oe (75.3 mg, 86%) as a white solid.

Experimental Section

N-[4-Ethoxy-2-(m-tolyl)quinazolin-7-yl]pivalamide (163pg): The general procedure C was followed using ethyl 4-pivalamidobenzimidate (161p) (62.1 mg, 0.25 mmol) and 3-(m-tolyl)-1,4,2-dioxazol-5-one (162g) (53.2 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 6/1) yielded 163pg (77.0 mg, 85%) as a white solid.

M. p. = 199─201 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.39 (s, 1H), 8.36 (s, 1H), 8.08 (d, J = 8.9 Hz, 1H),

Experimental Section

188

N-[4-Ethoxy-2-(4-methoxyphenyl)quinazolin-7-yl]pivalamide (163pf): The general procedure C was followed using ethyl 4-pivalamidobenzimidate (161p) (62.1 mg, 0.25 mmol) and 3-(4-methoxyphenyl)-1,4,2-dioxazol-5-one (162f) (57.9 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 6/1) yielded 163pf (81.0 mg, 85%) as a white solid.

M. p. = 211─213 ˚C. ¹H NMR (400 MHz, CDCl3) δ = 8.48 (d, J = 9.0 Hz, 2H), 8.01 (d, J = 8.8 Hz, 1H),

N-[2-(4-Chlorophenyl)-4-ethoxyquinazolin-7-yl]pivalamide (163pj): The general procedure C was followed using ethyl 4-pivalamidobenzimidate (161p) (62.1 mg, 0.25 mmol) and 3-(4-chlorophenyl)-1,4,2-dioxazol-5-one (162j) (59.3 mg, 0.30 mmol). Purification by coloumn chromatography on silica gel (n-hexane/EtOAc: 6/1) yielded 163pj (86.0 mg, 90%) as a white solid.

M. p. = 228─230 ˚C. ¹H NMR (300 MHz, CDCl3) δ = 8.48 (d, J = 8.6 Hz, 2H), 8.06 (d, J = 8.9 Hz, 1H), 8.02 (d, J = 2.1 Hz, 1H), 7.79 (dd, J = 8.9, 2.1 Hz, 1H), 7.66 (s, 1H), 7.45 (d, J = 8.6 Hz, 2H), 4.70 (q, J = 7.1 Hz, 2H), 1.55 (t, J = 7.1 Hz, 3H), 1.39 (s, 9H). ¹³C NMR (75 MHz, CDCl3) δ = 176.8 (Cq), 166.3 (Cq), 159.5 (Cq), 152.8 (Cq), 142.7 (Cq), 136.8 (Cq), 136.5 (Cq), 129.8 (CH), 128.5 (CH), 124.5 (Cq), 119.7 (CH), 115.9 (CH), 111.8 (CH), 62.8 (CH2), 39.9 (Cq), 27.6 (CH3), 14.4 (CH3). IR (ATR) ν = 3323, 2984, 1659,

Experimental Section

1579, 1437, 1324, 1205, 1089, 1014, 789 cm^-1. MS (ESI) m/z (relative intensity): 384 (100) [M+H]⁺, 406 (10) [M+Na]⁺. HR-MS (ESI) m/z calcd for C21H23N3O2 [M+H]⁺: 384.1473, found: 384.1476.

4-Ethoxy-2-phenethyl-7-(pyridin-2-yloxy)quinazoline (163qc): The general procedure C was followed using ethyl 4-(pyridin-2-yloxy)benzimidate (161q) (60.8 mg, 0.25 mmol) and 5-phenethyloxazol-2(5H)-one (162c) (57.3 mg, 0.30 mmol). Purification by column chromatography on silica gel (n-hexane/EtOAc: 10/1) yielded 163qc (75.2 mg, 81%) as a colorless oil.

1H NMR (300 MHz, CDCl3) δ = 8.25 (ddd, J = 5.0, 2.0, 0.8 Hz, 1H), 8.15 (dd, J = 8.9, 0.4 Hz, 1H), 7.78─7.72 (m, 1H), 7.51 (dd, J = 2.4, 0.6 Hz, 1H), 7.34─7.24 (m, 5H), 7.22─7.15 (m, 1H), 7.08 (dd, J = 7.3, 5.0 Hz, 1H), 7.04 (d, J = 8.4 Hz, 1H), 4.63 (q, J = 7.1 Hz, 2H), 3.28─3.18 (m, 4H), 1.49 (t, J = 7.1 Hz, 3H). ¹³C NMR (75 MHz, CDCl3) δ = 167.0 (Cq), 166.5 (Cq), 162.8 (Cq), 158.9 (Cq), 153.2 (Cq), 148.1 (CH), 141.9 (Cq), 139.9 (CH), 128.6 (CH), 128.4 (CH), 125.9 (CH), 125.3 (CH), 120.6 (CH), 119.7 (CH), 115.9 (CH), 112.9 (CH), 111.8 (Cq), 62.8 (CH2), 41.4 (CH2), 34.5 (CH2), 14.5 (CH3). IR (ATR) ν = 2979, 1622, 1569, 1416, 1340, 1238, 1135, 1104 cm^-1. MS (ESI) m/z (relative intensity): 372 (100) [M+H]⁺, 394 (10) [M+Na]⁺. HR-MS (ESI) m/z calcd for C23H22N3O2 [M+H]⁺: 372.1712, found: 372.1707.

4-Ethoxy-7-(pyridin-2-yloxy)-2-n-tridecylquinazoline (163qd): The general procedure C was followed using ethyl 4-(pyridin-2-yloxy)benzimidate (161q) (60.6 mg, 0.25 mmol), 5-tridecyloxazol-2(5H)-one (162d) (80.8 mg, 0.30 mmol). Purification by column chromatography on silica gel (n-hexane/EtOAc: 4/1) yielded 163qd (96.7 mg, 86%) as a colorless oil.

1H NMR (300 MHz, CDCl3) δ = 8.23 (ddd, J = 4.9, 2.0, 0.6 Hz, 1H), 8.14 (d, J = 8.9 Hz, 1H), 7.77─7.71 (m, 1H), 7.53 (s, 1H), 7.28 (dd, J = 8.9, 2.3 Hz, 1H), 7.06 (dd, J = 7.4, 4.9, 0.6 Hz, 1H), 7.02 (d, J = 8.2

Im Dokument Cobalt(III)- and Manganese(I)-Catalyzed C-H and C-C Activations (Seite 173-0)