Water → HCID 178451659, compound

HRID 64318Notes

Reaction equation

HRID 64318 reaction equation
[NH2:1][C:2]1[NH:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:9][CH:8]=2)[C:3]=1[C:20]#[N:21].C([O-])([O-])=O.[K+].[K+].Br[CH:29]1[C:34](=O)[CH2:33][CH2:32][N:31]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:30]1.O>CN(C=O)C.CC(=O)OCC>[C:20]([C:3]1[C:4]([C:7]2[CH:8]=[CH:9][C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)=[N:5][N:6]2[C:29]3[CH2:30][N:31]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:33][C:34]=3[NH:1][C:2]=12)#[N:21]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 106839701-tert-Butyloxycarbonyl-3-bromo-4-oxopiperidineHCID 178509389HCID 178509389, compound

Product 1

HCID 178451659HCID 178451659, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile (1.5 g, 5.4 mmol) and K2CO3 (2.24 g, 16.3 mmol) in 50 mL of DMF at 80° C. was stirred under N2 for 45 min before tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate (4.5 g, 16.3 mmol) was added in one portion. Then the mixture was stirred at 80° C. for 1 hr. After cooling down to RT, 150 mL of water and 150 mL of EA was added. Aqueous phase was further extracted with EA (100 mL×3). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated to get crude product which was chromatographed on 15 g of silica gel using DCM/MeOH (400/1 to 200/1) as eluant to afford 850 mg (35%) of tert-butyl 3-cyano-2-(4-phenoxyphenyl)-5,6-dihydro-4H-pyrazolo[5′,1′:2,3]imidazo[4,5-c]pyridine-7(8H)-carboxylate as an off-white solid. MS (ESI) m/e [M+1]+ 455.9.

Workup

  1. additionwas added in one portion
  2. temperatureAfter cooling down to RT
  3. extractionAqueous phase was further extracted with EA (100 mL×3)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto get crude product which
  8. customwas chromatographed on 15 g of silica gel

Sources & evidence

ORD record
ord-584d0200a4824055a28533d1e5226eaf
Source dataset
uspto-grants-2016_09
Patent number
US09447106B2

Reaction notes

Loading…