Dimethylformamide → 5-(1-(2-cyano-1-cyclopropylethyl)-1H-pyrazol-4-yl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine-3-carbonitrile

HRID 1852979Notes

Reaction equation

HRID 1852979 reaction equation
[CH:1]1([CH:4]([N:8]2[CH:12]=[C:11]([C:13]3[N:18]4[C:19](I)=[CH:20][N:21]=[C:17]4[CH:16]=[C:15]([C:23]4[CH:24]=[N:25]N(C)[CH:27]=4)[N:14]=3)[CH:10]=[N:9]2)[CH2:5][C:6]#[N:7])[CH2:3][CH2:2]1.[C:29]([Cu])#[N:30].[CH3:32][N:33](C=O)C>CCOC(C)=O.[NH4+].[OH-]>[C:6]([CH2:5][CH:4]([N:8]1[CH:12]=[C:11]([C:13]2[N:18]3[C:19]([C:32]#[N:33])=[CH:20][N:21]=[C:17]3[CH:16]=[C:15]([C:23]3[CH:24]=[N:25][N:30]([CH3:29])[CH:27]=3)[N:14]=2)[CH:10]=[N:9]1)[CH:1]1[CH2:3][CH2:2]1)#[N:7]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 866853053-cyclopropyl-3-(4-(3-iodo-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrileHCID 178418546HCID 178418546, compound

Product 1

HCID 674587565-(1-(2-cyano-1-cyclopropylethyl)-1H-pyrazol-4-yl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine-3-carbonitrileYield 62%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
160 °C

Procedure

In a microwave safe flask, 3-cyclopropyl-3-(4-(3-iodo-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile (22.4 mg, 0.0463 mmol) and cyanocopper (4.56 mg, 0.0509 mmol) were suspended in DMF (463 μL, 0.0463 mmol). The reaction mixture was heated at 160° C. for 1 hour. The reaction mixture was cooled and diluted in EtOAc and 10% NH4OH (10 mL). The mixture was separated and the aqueous layer extracted with EtOAc. The combined organic layers were washed with brine, dried with MgSO4, filtered and concentrated in vacuo. Purification using preparative TLC in 15% MeOH/EtOAc afforded 5-(1-(2-cyano-1-cyclopropylethyl)-1H-pyrazol-4-yl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine-3-carbonitrile (11.0 mg, 62.0% yield). MS (apci) m/z=384.4 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customThe mixture was separated
  3. extractionthe aqueous layer extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification

Sources & evidence

ORD record
ord-caaf61609c6c499aacf504f0bceee1fe
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

Loading…