1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-cyclopentyl-3-(4-(7-(4-morpholinophenyl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

HRID 1853045Notes

Reaction equation

HRID 1853045 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[N:11]3[CH:12]=[CH:13][N:14]=[C:10]3[CH:9]=[C:8]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[CH:17][CH:16]=3)[N:7]=2)[CH:3]=[N:2]1.[CH:27]1([CH:32]=[CH:33][C:34]#[N:35])[CH2:31][CH2:30][CH2:29][CH2:28]1.N1CCCN2CCCCCC=12>CN(C=O)C>[CH:27]1([CH:32]([N:1]2[CH:5]=[C:4]([C:6]3[N:11]4[CH:12]=[CH:13][N:14]=[C:10]4[CH:9]=[C:8]([C:15]4[CH:20]=[CH:19][C:18]([N:21]5[CH2:26][CH2:25][O:24][CH2:23][CH2:22]5)=[CH:17][CH:16]=4)[N:7]=3)[CH:3]=[N:2]2)[CH2:33][C:34]#[N:35])[CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 534011163-Cyclopentylprop-2-enenitrileHCID 86685325HCID 86685325, compound

Product 1

HCID 674582543-cyclopentyl-3-(4-(7-(4-morpholinophenyl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrileYield 46.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-(5-(1H-Pyrazol-4-yl)imidazo[1,2-c]pyrimidin-7-yl)phenyl)morpholine (0.0300 g, 0.0866 mmol) and 3-cyclopentylaerylonitrile (Table 1, compound g; 0.0175 g, 0.144 mmol) were suspended in DMF (3 mL) and 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (0.0324 mL, 0.217 mmol) added in one portion. The reaction mixture was stirred at ambient temperature over the weekend. The reaction mixture was partitioned between saturated aqueous 1 N NaOH and EtOAc. The solids were isolated by filtration. The organics were washed with brine, dried over MgSO4 and concentrated under reduced pressure to afford the crude material, which was purified by flash column chromatography (eluant: 0.5-3% (9:1, MeOH:NH4OH)/DCM) to provide 3-cyclopentyl-3-(4-(7-(4-morpholinophenyl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile (0.0190 g, 0.04064 mmol, 46.9% yield). MS (apci) m/z=468.2 (M+H).

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous 1 N NaOH and EtOAc
  2. customThe solids were isolated by filtration
  3. washThe organics were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude material, which
  7. customwas purified by flash column chromatography (eluant: 0.5-3% (9:1, MeOH:NH4OH)/DCM)

Sources & evidence

ORD record
ord-c80c5e20c59d4117a78a544fa461f441
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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