Dimethylformamide → N-(3-Chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine

HRID 712378Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([OH:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].C([O-])([O-])=O.[K+].[K+].Br[CH2:30][CH2:31][CH2:32][Cl:33].CN(C=O)C>O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([O:20][CH2:30][CH2:31][CH2:32][Cl:33])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

Conditions

Temperature: 40 °C

Procedure

A suspension of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (20.00 g), K2CO3 (10.37 g), KI (1.04 g), 1-bromo-3-chloropropane (7.50 mL) and DMF (150 mL) was stirred at 40° C. for 6 h. The reaction mixture was poured into water and filtered. The filter residue was purified by a silica gel column chromatography (eluting agent: EA) to give the title compound as pale yellow liquid (22.05 g, 89.00%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 396.1 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.01 (m, 2H), 3.68 (t, J=4.2 Hz, 2H), 4.00 (s, 3H), 4.10 (t, J=4.2 Hz, 2H), 6.80 (s, 1H), 7.16 (s, 1H), 7.26 (s, 1H), 7.30 (s, 1H), 7.47 (s, 1H), 8.64 (s, 1H) ppm.

Workup

filtrationfiltered
customThe filter residue was purified by a silica gel column chromatography (eluting agent: EA)

Sources & evidence

ORD record: ord-89ddef0b40b744998cd8b7dc428daae3
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181277B2

Reaction notes

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