Sodium hydride → 1-(4-Amino-5-fluoro-7-quinazolinyl)-1,5,6,7-tetrahydro-3,6,6-trimethyl-4H-indol-4-one

HRID 2244060Notes

Reaction equation

HRID 2244060 reaction equation
[CH3:1][C:2]1[C:10]2[C:9](=[O:11])[CH2:8][C:7]([CH3:13])([CH3:12])[CH2:6][C:5]=2[NH:4][CH:3]=1.[H-].[Na+].[F:16][C:17]1[CH:26]=[C:25](F)[CH:24]=[C:23]2[C:18]=1[C:19]([NH2:28])=[N:20][CH:21]=[N:22]2>CN(C=O)C>[NH2:28][C:19]1[C:18]2[C:23](=[CH:24][C:25]([N:4]3[C:5]4[CH2:6][C:7]([CH3:13])([CH3:12])[CH2:8][C:9](=[O:11])[C:10]=4[C:2]([CH3:1])=[CH:3]3)=[CH:26][C:17]=2[F:16])[N:22]=[CH:21][N:20]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 248207983,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-oneHCID 25059435HCID 25059435, compound

Product 1

HCID 250612361-(4-Amino-5-fluoro-7-quinazolinyl)-1,5,6,7-tetrahydro-3,6,6-trimethyl-4H-indol-4-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3,6,6-Trimethyl-1,5,6,7-tetrahydro-indol-4-one (0.61 mmol, 107.6 mg) is dissolved in 5 mL DMF. To this solution is added sodium hydride (60% suspension in mineral oil) (0.77 mmol, 30.8 mg) and the mixture is stirred at rt for 5 min. and then 5,7-Difluoro-quinazolin-4-ylamine (0.55 mmol, 100 mg) is added. The reaction is stirred at 50° C. for 22 h. The reaction is cooled and quenched by pouring into 100 ml sat. NH4Cl aq. and extracted 3 times with 20 mL CH2Cl2. The combined organics are dried with Na2SO4, concentrated, and purified by silica gel chromatography on Biotage using a gradient of 0-15% MeOH in CH2Cl2. 1-(4-Amino-5-fluoro-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one is isolated (35 mg, LC/MS m/z=339 [M+H]+) as a white powder.

Workup

  1. stirringThe reaction is stirred at 50° C. for 22 h
  2. temperatureThe reaction is cooled
  3. customquenched
  4. additionby pouring into 100 ml sat. NH4Cl aq.
  5. extractionextracted 3 times with 20 mL CH2Cl2
  6. dry with materialThe combined organics are dried with Na2SO4
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography on Biotage

Sources & evidence

ORD record
ord-dfdb8ca33eff4e47aea62b20aac6b5d5
Source dataset
uspto-grants-2010_03
Patent number
US07678803B2

Reaction notes

Loading…