2-Chloro-6,7-dimethoxy-4-quinazolinamine → 4-[1-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperidin-4-ylamino]-benzoic acid tert-butyl ester

HRID 1274121Notes

Reaction equation

[C:1]([O:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:21][C:22]1[C:31]2[C:26](=[CH:27][C:28]([O:34][CH3:35])=[C:29]([O:32][CH3:33])[CH:30]=2)[N:25]=[C:24](Cl)[N:23]=1>C(O)CC(C)C>[C:1]([O:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([C:24]3[N:23]=[C:22]([NH2:21])[C:31]4[C:26](=[CH:27][C:28]([O:34][CH3:35])=[C:29]([O:32][CH3:33])[CH:30]=4)[N:25]=3)[CH2:16][CH2:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 120 °C

Procedure

Compound 49 (0.57 g, 2.1 mmol) was added to a solution of 4-amino-2-chloro-6,7-dimethoxy quinazoline (0.45 g, 1.9 mmol) in isoamyl alcohol (3-methyl-1-butanol) (20 mL) at 25° C. The mixture was stirred at 120° C. for 12 h. The reaction mixture was cooled to room temperature and the desired product was filtered and rinsed with acetone to give 0.57 g (59%) of the title compound: TLC (Rf =0.41; 80% EtOAc/hexanes); 1H NMR (DMSO) δ 12.20 (br s, 1H), 8.66 (br, 2H), 7.76 (s, 1H), 7.66 (d, 2H, J=8.7), 7.53 (s, 1H), 6.67 (d, 2H, J=8.7), 6.51 (d, 1H, J=7.4), 4.56 (d, 2H, J=13.6), 3.90 (s, 3H), 3.86 (s, 3H), 3.76 (m, 1H), 3.46 (m, 2H), 2.07 (d, 2H, J=11.1), 1.52 (s, 9H), 1.44 (m, 2H); 13C NMR (DMSO) δ 165.3, 161.4, 155.3, 151.4, 151.1, 146.8, 136.4, 131.0, 117.8, 111.3, 105.0, 101.6, 99.2, 79.1, 56.3, 56.1, 48.0, 43.4, 31.0, 28.1; HRMS (FAB) m/z 480.2616 (M+H)+ (C26H33N5O4 requires 480.2611); Anal. (C26H33N5O4 ·1HCl) C, H, N.

Workup

temperatureThe reaction mixture was cooled to room temperature
filtrationthe desired product was filtered
washrinsed with acetone

Sources & evidence

ORD record: ord-c6e50ebbd1c64f748f6cc91934499cdd
Source dataset: uspto-grants-2000_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06156758

Reaction notes

Loading…