Acetonitrile → 3-Cyclopropyl-3-(3-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

HRID 1853058

Reaction equation

HRID 1853058 reaction equation
Cl.[CH3:2][N:3]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]3[CH:18]=[CH:17][NH:16][N:15]=3)[N:11]3[CH:19]=[CH:20][N:21]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1.[CH:22]1([CH:25]=[CH:26][C:27]#[N:28])[CH2:24][CH2:23]1.C(#N)C.C1CCN2C(=NCCC2)CC1>>[CH:22]1([CH:25]([N:16]2[CH:17]=[CH:18][C:14]([C:12]3[N:11]4[CH:19]=[CH:20][N:21]=[C:10]4[CH:9]=[C:8]([C:6]4[CH:5]=[N:4][N:3]([CH3:2])[CH:7]=4)[N:13]=3)=[N:15]2)[CH2:26][C:27]#[N:28])[CH2:24][CH2:23]1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 670567823-CyclopropylacrylonitrileHCID 178478909HCID 178478909, compound

Product 1

HCID 682307973-Cyclopropyl-3-(3-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrileYield 17.5%

Conditions

Temperature
45 °C

Procedure

7-(1-Methyl-1H-pyrazol-4-yl)-5-(1H-pyrazol-3-yl)imidazo[1,2-c]pyrimidine hydrochloride (Example 129, Step C, 50.2 mg, 0.148 mmol) and 3-cyclopropylacrylonitrile (Preparation B; 69.1 mg, 0.742 mmol) were suspended in acetonitrile (742 μL, 0.148 mmol). DBU (88.8 μL, 0.594 mmol) was added to the reaction mixture and heated at 45° C. for 15 hours. The reaction mixture was purified by reverse phase HPLC using a 0-100% acetonitrile/water gradient. The resultant solid was diluted in Et2O, sonicated, filtered and washed with Et2O to afford the title compound as a light yellow solid (9.3 mg, 17% yield). MS (apci) m/z=359.2 (M+H).

Workup

  1. customThe reaction mixture was purified by reverse phase HPLC
  2. additionThe resultant solid was diluted in Et2O
  3. customsonicated
  4. filtrationfiltered
  5. washwashed with Et2O

Sources & evidence

ORD record
ord-b6d64f41f3874e56a935d3b0ff34dff9
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Linked notes

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