Triethylamine → (3-{3-[1-(4-Amino-3-bromo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}azetidin-1-yl)acetonitrile

HRID 1499783Notes

Reaction equation

HRID 1499783 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[C:6]([O:26][CH3:27])=[C:7]([CH:13]([N:15]3[C:19]4=[N:20][CH:21]=[N:22][C:23]([NH2:24])=[C:18]4[C:17]([Br:25])=[N:16]3)[CH3:14])[CH:8]=[C:9]([Cl:12])[C:10]=2[CH3:11])[CH2:2]1.[CH2:28]([N:30](CC)CC)[CH3:29].BrCC#N>C(#N)C.CN(C=O)C>[NH2:24][C:23]1[N:22]=[CH:21][N:20]=[C:19]2[N:15]([CH:13]([C:7]3[C:6]([O:26][CH3:27])=[C:5]([CH:3]4[CH2:4][N:1]([CH2:29][C:28]#[N:30])[CH2:2]4)[C:10]([CH3:11])=[C:9]([Cl:12])[CH:8]=3)[CH3:14])[N:16]=[C:17]([Br:25])[C:18]=12

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 11534BromoacetonitrileHCID 866777091-[1-(3-Azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 86677710(3-{3-[1-(4-Amino-3-bromo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}azetidin-1-yl)acetonitrileYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6342AcetonitrileSolvent

Procedure

To a mixture of 1-[1-(3-azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.2 mmol) and triethylamine (37 μL, 0.27 mmol) in acetonitrile (3 mL) was added bromoacetonitrile (19 μL, 0.27 mmol). The resulting mixture was stirred at room temp. After an hour, the reaction mixture was still cloudy with not all of the material in solution. Several drops of DMF were added which allowed for a clear solution. The mixture was stirred overnight at room temperature and then most of the solvents were evaporated. The resulting residue was purified on silica gel (eluted with 0-10% MeOH in dichloromethane) to give 29 mg (30%) of the desired product. LCMS calculated for C20H22BrClN7O (M+H)+: m/z=490.1; Found: 490.1.

Workup

  1. waitAfter an hour
  2. stirringThe mixture was stirred overnight at room temperature
  3. custommost of the solvents were evaporated
  4. customThe resulting residue was purified on silica gel (eluted with 0-10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-59c8863fd65d457dbd58c956f278de6b
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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