Tetrahydrofuran → (3-[2-[2-Amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-3-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazol-1-yl)acetonitrile

HRID 2090387Notes

Reaction equation

HRID 2090387 reaction equation
CC(C)([O-])C.[K+].C1COCC1.[CH3:12][N:13]1[CH2:18][CH2:17][N:16]([C:19]2[CH:24]=[C:23]([N:25]3[CH:34]([CH3:35])[CH2:33][C:32]4[C:27](=[CH:28][C:29]([C:36]5[CH:40]=[CH:39][NH:38][N:37]=5)=[CH:30][CH:31]=4)[CH2:26]3)[N:22]=[C:21]([NH2:41])[N:20]=2)[CH2:15][CH2:14]1.Br[CH2:43][C:44]#[N:45]>CN(C=O)C>[NH2:41][C:21]1[N:22]=[C:23]([N:25]2[CH:34]([CH3:35])[CH2:33][C:32]3[C:27](=[CH:28][C:29]([C:36]4[CH:40]=[CH:39][N:38]([CH2:43][C:44]#[N:45])[N:37]=4)=[CH:30][CH:31]=3)[CH2:26]2)[CH:24]=[C:19]([N:16]2[CH2:15][CH2:14][N:13]([CH3:12])[CH2:18][CH2:17]2)[N:20]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11534BromoacetonitrileHCID 23665647Potassium tert-butoxideHCID 1784218914-(4-methylpiperazin-1-yl)-6-[3-methyl-7-(1H-pyrazol-3-yl)-3,4-dihydroisoquinolin-2(1H)-yl]pyrimidin-2-amine

Product 1

HCID 46701050(3-[2-[2-Amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-3-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazol-1-yl)acetonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium tert-butoxide in THF (1.0 M, 74.2 uL, 0.0742 mmol) was added to a solution of 4-(4-methylpiperazin-1-yl)-6-[3-methyl-7-(1H-pyrazol-3-yl)-3,4-dihydroisoquinolin-2(1H)-yl]pyrimidin-2-amine (15.0 mg, 0.0371 mmol) in DMF (0.3 mL) and stirred at r.t. for 10 min, and then bromoacetonitrile (3.71 uL, 0.0556 mmol) was added. The mixture was stirred at r.t. for 1 h. LCMS showed the reaction was complete. The mixture was purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+: m/z=444.2.

Workup

  1. stirringThe mixture was stirred at r.t. for 1 h
  2. customThe mixture was purified by RP-HPLC (pH=10)

Sources & evidence

ORD record
ord-b515c075cef14035a65c1141df139791
Source dataset
uspto-grants-2013_05
Patent number
US08436008B2

Reaction notes

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