Lithium Hexamethyldisilazide → 4-(8-(3-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-ylamino)-7-methylquinazolin-4-ylamino)benzonitrile

HRID 1042287Notes

Reaction equation

HRID 1042287 reaction equation
[CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[N:15][C:16]([C:17]4[C:18](F)=[N:19][CH:20]=[CH:21][CH:22]=4)=[C:11]3[CH:10]=[N:9]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+].N.CO>C1COCC1.CC(O)=O.CO>[CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[N:15][C:16]([C:17]4[C:18]([NH:26][C:27]5[C:28]([CH3:46])=[CH:29][CH:30]=[C:31]6[C:36]=5[N:35]=[CH:34][N:33]=[C:32]6[NH:37][C:38]5[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=5)=[N:19][CH:20]=[CH:21][CH:22]=4)=[C:11]3[CH:10]=[N:9]2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 2733832Lithium HexamethyldisilazideHCID 21705897Ammonia methanolHCID 687253434-(8-Amino-7-methylquinazolin-4-ylamino)benzonitrileHCID 68743622HCID 68743622, compound

Product 1

HCID 687800684-(8-(3-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-ylamino)-7-methylquinazolin-4-ylamino)benzonitrile

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of 1-(4-methoxybenzyl)-4-(2-fluoropyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine (150 mg, 447 mmol) and 4-(8-amino-7-methylquinazolin-4-ylamino)benzonitrile (135 mg, 492 mmol) in THF (3 ml) was sonicated until the solid became a fine powder. To this mixture was added lithium bis(trimethylsilyl)amide, 1.0 M solution in THF) (1476 μl, 1476 mmol) slowly. The mixture was stirred at it for 4 hr (LCMS: some SM) and then heated in a microwave synthesizer at 60° C. for 20 min The mixture was poured into MeOH (15 ml) and AcOH (0.5 ml) was added and then NH3/MeOH (2 M, 20 mL) was added. Solvent was removed in vacuo. The product was purified by flash chromatography eluting with MeOH/DCM (1-5%) to give 4-(8-(3-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-ylamino)-7-methylquinazolin-4-ylamino)benzonitrile. MS Found (ESI pos. ion) m/z 591 (M+H+).

Workup

  1. customwas sonicated until the solid
  2. additionwas added
  3. customSolvent was removed in vacuo
  4. customThe product was purified by flash chromatography
  5. washeluting with MeOH/DCM (1-5%)

Sources & evidence

ORD record
ord-1070b2a186cd40bca7132850afad1408
Source dataset
uspto-grants-2013_10
Patent number
US08557830B2

Reaction notes

Loading…