Acetic Acid → 3-cyclopropyl-3-(4-(3-fluoro-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

HRID 1853078Notes

Reaction equation

HRID 1853078 reaction equation
[CH:1]1([CH:4]([N:8]2[CH:12]=[C:11]([C:13]3[N:18]4[CH:19]=[CH:20][N:21]=[C:17]4[CH:16]=[C:15]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[N:14]=3)[CH:10]=[N:9]2)[CH2:5][C:6]#[N:7])[CH2:3][CH2:2]1.[B-](F)(F)(F)[F:29].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1.C(O)(=O)C>CC#N>[CH:1]1([CH:4]([N:8]2[CH:12]=[C:11]([C:13]3[N:18]4[C:19]([F:29])=[CH:20][N:21]=[C:17]4[CH:16]=[C:15]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[N:14]=3)[CH:10]=[N:9]2)[CH2:5][C:6]#[N:7])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 2724933SelectfluorHCID 534974533-cyclopropyl-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

Product 1

HCID 682311903-cyclopropyl-3-(4-(3-fluoro-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrileYield 20%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

3-Cyclopropyl-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile (Example 2; 0.200 g, 0.558 mmol), Selectfluor® (0.395 g, 1.12 mmol) and acetic acid (0.320 mL, 5.58 mmol) were suspended in MeCN (20 mL) and heated to 80° C. overnight. The reaction mixture was cooled to ambient temperature and the reaction mixture partitioned between saturated aqueous sodium hydrogen carbonate and ethyl acetate. The combined organic extracts were washed with brine, dried, magnesium sulfate and concentrated under reduced pressure to afford the crude material, which was purified by flash column chromatography, eluting with 1-2% (9:1 MeOH:NH4OH)/dichloromethane to provide the 3-cyclopropyl-3-(4-(3-fluoro-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile (0.042 g, 0.112 mmol, 20% yield). MS (apci) m/z=377.1 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe reaction mixture partitioned between saturated aqueous sodium hydrogen carbonate and ethyl acetate
  3. washThe combined organic extracts were washed with brine
  4. customdried
  5. concentrationmagnesium sulfate and concentrated under reduced pressure
  6. customto afford the crude material, which
  7. customwas purified by flash column chromatography
  8. washeluting with 1-2% (9:1 MeOH:NH4OH)/dichloromethane

Sources & evidence

ORD record
ord-c2624f6129644025a1bb4cfe42e5e706
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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