Sodium hydride → 7-Chloro-3-[(6,7-dimethoxy-quinazolin-4-ylamino)-methyl]-1-phenyl-1H-quinolin-4-one

HRID 1887944Notes

Reaction equation

HRID 1887944 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[NH2:15].[H-].[Na+].Br[CH2:19][C:20]1[C:29](=[O:30])[C:28]2[C:23](=[CH:24][C:25]([Cl:31])=[CH:26][CH:27]=2)[N:22]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:21]=1>CN(C=O)C>[Cl:31][C:25]1[CH:24]=[C:23]2[C:28]([C:29](=[O:30])[C:20]([CH2:19][NH:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)=[CH:21][N:22]2[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 130604516,7-Dimethoxyquinazolin-4-amineHCID 866757643-bromomethyl-7-chloro-1-phenyl-1H-quinolin-4-one

Product 1

HCID 712086637-Chloro-3-[(6,7-dimethoxy-quinazolin-4-ylamino)-methyl]-1-phenyl-1H-quinolin-4-oneYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

In a 25 mL round-bottomed flask, 6,7-dimethoxyquinazolin-4-amine (69.3 mg, 0.338 mmol) was combined with DMF (2.0 mL) to give a colorless solution. Sodium hydride (60% suspension in oil) (23.0 mg, 0.575 mmol) was added in three portions. The reaction mixture was stirred at room temperature for 15 min. After this time, the reaction mixture was a yellow solution. A DMF solution of the crude 3-bromomethyl-7-chloro-1-phenyl-1H-quinolin-4-one was next added dropwise via a syringe. The reaction mixture was stirred at 50° C. for 3 hr. After this time, TLC is quite messy, but LC/MS gives a strong peak for the desired product (approx 44%). The reaction mixture was cooled to room temperature, then was partitioned between water and ethyl acetate. The organic layer was dried over Na2SO4, filtered, then concentrated to furnish a brown oil. This crude product was dissolved in methylene chloride, then this solution was concentrated over silica gel. The silica gel-supported crude product was loaded onto a 80 gram SiliCycle column. Flash chromatography (2.5% methanol-methylene chloride ramped to 6% methanol-methylene chloride) afforded 7-chloro-3-[(6,7-dimethoxy-quinazolin-4-ylamino)-methyl]-1-phenyl-1H-quinolin-4-one. MS calcd. for C26H21ClN4O3 [(M+H)+] 472.9, obsd. 473.0.

Workup

  1. customto give a colorless solution
  2. stirringThe reaction mixture was stirred at 50° C. for 3 hr

Sources & evidence

ORD record
ord-5cddbfcc0e36455195a3e821a68a920c
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Reaction notes

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