Water → N-(3-chloro-4-fluoro-phenyl)-7-(2-methoxyethoxy)-6-nitro-quinazolin-4-amine

HRID 2199350Notes

Reaction equation

[CH3:1][O:2][CH2:3][CH2:4][OH:5].[H-].[Na+].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](F)=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].O>CS(C)=O>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]

Participants

Conditions

Temperature: 40 °C

Procedure

2-methoxyethanol (152 mg, 2 mmol) was dissolved in 30 mL of dimethyl sulfoxide in an ice-water bath, followed by addition of 60% sodium hydride (80 mg, 2 mmol). The mixture was warmed up to 40° C. and stirred for 2 hours, then N-(3-chloro-4-fluoro-phenyl)-7-fluoro-6-nitro-quinazolin-4-amine 8a (336 mg, 1 mmol) was added. The reaction mixture was stirred for 4 hours at 40° C., then warmed up to 50° C. and stirred for 12 hours. The reaction mixture was added with water (20 mL), filtered and the filter cake was washed with water (50 mL), dried under vacuum to obtain the title compound N-(3-chloro-4-fluoro-phenyl)-7-(2-methoxyethoxy)-6-nitro-quinazolin-4-amine 8b (392 mg, yield 100%) as a yellow solid, which was directly used in the next step.

Workup

stirringThe reaction mixture was stirred for 4 hours at 40° C.
temperaturewarmed up to 50° C.
stirringstirred for 12 hours
filtrationfiltered
washthe filter cake was washed with water (50 mL)
customdried under vacuum

Sources & evidence

ORD record: ord-cfc3daeb8e3f4038af0018f2f02d2d4f
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09358227B2

Reaction notes

Loading…