Sodium hydride → 1-(4-Amino-pyrido[3,2-d]pyrimidin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one

HRID 2244082Notes

Reaction equation

HRID 2244082 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[C:17]1[CH:26]=[N:25][C:24]2[C:23]([NH2:27])=[N:22][CH:21]=[N:20][C:19]=2[CH:18]=1>CN(C=O)C>[NH2:27][C:23]1[C:24]2[N:25]=[CH:26][C:17]([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:18][C:19]=2[N:20]=[CH:21][N:22]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 248207983,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-oneHCID 250596967-Fluoro-pyrido[3,2-d]pyrimidin-4-amine

Product 1

HCID 250614931-(4-Amino-pyrido[3,2-d]pyrimidin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3,6,6-Trimethyl-1,5,6,7-tetrahydro-indol-4-one (0.181, 32 mg) is dissolved in 1 mL DMF. To this solution is added sodium hydride (60% suspension in mineral oil, 0.229 mmol, 9.18 mg) and the mixture is stirred at rt for 5 min. and then 7-Fluoro-pyrido[3,2-d]pyrimidin-4-ylamine (0.164 mmol, 27 mg) is added. The reaction mixture is stirred at 50° C. for 22 h. The reaction mixture is cooled and quenched by pouring into 20 mL sat. NH4Cl aq. and extracted 3 times with 5 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 DCM. 1-(4-Amino-pyrido[3,2-d]pyrimidin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one is isolated (12 mg, LC/MS m/z=322 [M+H]+) as a white powder.

Workup

  1. stirringThe reaction mixture is stirred at 50° C. for 22 h
  2. temperatureThe reaction mixture is cooled
  3. customquenched
  4. additionby pouring into 20 mL sat. NH4Cl aq.
  5. extractionextracted 3 times with 5 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-f3d8f88d6fd640d0802dfecc24927b16
Source dataset
uspto-grants-2010_03
Patent number
US07678803B2

Reaction notes

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