Dimethylformamide → 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-6-chloro-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrile

HRID 1499927Notes

Reaction equation

HRID 1499927 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[N:14][C:15]=2[NH2:17])[NH:10][N:9]=1.[Cl:18][C:19]1[C:24]([C:25]#[N:26])=[C:23]([N:27]2[CH2:30][CH:29]([O:31][CH3:32])[CH2:28]2)[C:22]([O:33][CH2:34][CH3:35])=[C:21]([CH:36](Cl)[CH3:37])[CH:20]=1.CN(C)C=O>CCOC(C)=O>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([CH:36]([C:21]3[CH:20]=[C:19]([Cl:18])[C:24]([C:25]#[N:26])=[C:23]([N:27]4[CH2:30][CH:29]([O:31][CH3:32])[CH2:28]4)[C:22]=3[O:33][CH2:34][CH3:35])[CH3:37])[N:9]=[C:8]([CH3:7])[C:16]=12

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 866778446-Chloro-4-(1-chloroethyl)-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrileHCID 178434474HCID 178434474, compound

Product 1

HCID 715090894-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-6-chloro-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrileYield 20%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Cesium carbonate (50 mg, 0.2 mmol) was added to a mixture of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (16 mg, 0.10 mmol) and 6-chloro-4-(1-chloroethyl)-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrile (30 mg, 0.09 mmol) in N,N-dimethylformamide (3 mL, 40 mmol) and the reaction was stirred at 80° C. overnight. The mixture was diluted with EtOAc, washed with water, brine, dried over Na2SO4, filtered and concentrated the crude product. The product was purified was purified by prep HPLC on a C-18 column eluting water:acetonitrile gradient buffered pH 10 to give the title compound as a white amorphous solid (0.007 g, 20%). The product was isolated as a racemic mixture. LCMS calculated for C21H25ClN7O2(M+H)+: m/z=442.1; found: 442.1. 1H NMR (400 MHz, DMSO-d6) δ 8.11 (s, 1H), 6.80 (s, 1H), 6.18 (d, J=7.1 Hz, 1H), 4.58-4.44 (m, 2H), 4.18 (m, 1H), 4.13-4.01 (m, 2H), 3.81-3.62 (m, 2H), 3.23 (s, 3H), 2.55 (s, 3H), 1.69 (d, J=7.1 Hz, 3H), 1.35 (t, J=7.0 Hz, 3H).

Workup

  1. washwashed with water, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated the crude product
  5. customThe product was purified
  6. customwas purified by prep HPLC on a C-18 column
  7. washeluting water

Sources & evidence

ORD record
ord-4fde2fc04fa74f73a7dfa6ccf5c1debd
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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