Acetic Acid → HCID 68725159, compound

HRID 1042276Notes

Reaction equation

HRID 1042276 reaction equation
[CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][N:8]2[CH:16]=[N:15][C:14]3[C:9]2=[N:10][CH:11]=[N:12][C:13]=3[C:17]2[C:18](F)=[N:19][CH:20]=[CH:21][CH:22]=2)=[CH:5][CH:4]=1.[NH2:26][C:27]1[C:28]([CH3:46])=[CH:29][CH:30]=[C:31]2[C:36]=1[N:35]=[CH:34][N:33]=[C:32]2[NH:37][C:38]1[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].CC(O)=O>C1COCC1.CO>[CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][N:8]2[CH:16]=[N:15][C:14]3[C:9]2=[N:10][CH:11]=[N:12][C:13]=3[C:17]2[C:18]([NH:26][C:27]3[C:28]([CH3:46])=[CH:29][CH:30]=[C:31]4[C:36]=3[N:35]=[CH:34][N:33]=[C:32]4[NH:37][C:38]3[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=3)=[N:19][CH:20]=[CH:21][CH:22]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 2733832Lithium HexamethyldisilazideHCID 59627379HCID 59627379, compoundHCID 687253434-(8-Amino-7-methylquinazolin-4-ylamino)benzonitrile

Product 1

HCID 68725159HCID 68725159, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 9-(4-methoxybenzyl)-6-(2-fluoropyridin-3-yl)-9H-purine (146 mg, 436 μmol) and 4-(8-amino-7-methylquinazolin-4-ylamino)benzonitrile (120 mg, 436 μmol) in THF (4 mL) was sonicated until all solids became a fine powder. Lithium bis(trimethylsilyl)amide (1.0 M solution in THF; 1.53 mL, 1.53 mmol) was added dropwise with stirring (all solids dissolved and then some solid appeared again). The mixture was stirred at rt for 10 min and then heated in a microwave at 140° C. for 30 min. The mixture was poured into AcOH (0.5 mL) in MeOH (20 mL) and the mixture was stirred for 10 min. Solvent was removed and the product was purified by flash chromatography eluting with MeOH/DCM (2-5%) to give 4-(8-(3-(9-(4-methoxybenzyl)-9H-purin-6-yl)pyridin-2-ylamino)-7-methylquinazolin-4-ylamino)benzonitrile. MS (ESI, pos. ion) m/z: 591.2 [M+H]+

Workup

  1. customwas sonicated until all solids
  2. dissolutiondissolved
  3. stirringThe mixture was stirred at rt for 10 min
  4. stirringthe mixture was stirred for 10 min
  5. customSolvent was removed
  6. customthe product was purified by flash chromatography
  7. washeluting with MeOH/DCM (2-5%)

Sources & evidence

ORD record
ord-d6186c49083d4cb69ddb6d342b6a411f
Source dataset
uspto-grants-2013_10
Patent number
US08557830B2

Reaction notes

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