Ammonia → HCID 86686376, compound

HRID 1043945Notes

Reaction equation

HRID 1043945 reaction equation
C1N=C[N:3](C(N2C=NC=C2)=O)C=1.[F:13][C:14]1[CH:19]=[C:18]([C:20]2[C:25]([CH3:26])=[CH:24][N:23]=[C:22]([O:27][CH3:28])[C:21]=2[CH3:29])[CH:17]=[CH:16][C:15]=1[C:30]1[N:34]([C@H:35]2[CH2:39][CH2:38][O:37][CH2:36]2)[N:33]=[CH:32][C:31]=1[C:40]([OH:42])=O.N>CN(C=O)C>[F:13][C:14]1[CH:19]=[C:18]([C:20]2[C:25]([CH3:26])=[CH:24][N:23]=[C:22]([O:27][CH3:28])[C:21]=2[CH3:29])[CH:17]=[CH:16][C:15]=1[C:30]1[N:34]([C@H:35]2[CH2:39][CH2:38][O:37][CH2:36]2)[N:33]=[CH:32][C:31]=1[C:40]([NH2:3])=[O:42]

Participants

5

Reactant 3

HCID 222Ammonia2×HCID 682631,1'-CarbonyldiimidazoleHCID 866863755-[2-fluoro-4-(2-methoxy-3,5-dimethylpyridin-4-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylic acid

Product 1

HCID 86686376HCID 86686376, compoundYield 96.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

CDI (21.4 g) was added at one time to a solution of 5-[2-fluoro-4-(2-methoxy-3,5-dimethylpyridin-4-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylic acid (38.7 g) in DMF (290 mL) at room temperature, and the mixture was stirred at room temperature for 95 minutes. 28% aqueous ammonia (95 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 35 minutes. 28% aqueous ammonia (95 mL) was added again to the reaction mixture, and the mixture was stirred at room temperature for 90 minutes. The reaction mixture was concentrated under reduced pressure. Chloroform (250 mL) and water (80 mL) were added to the resulting residue, and the organic layer was separated. The aqueous layer was re-extracted with chloroform (50 mL). The combined organic layers were sequentially washed with a saturated aqueous ammonium chloride solution (60 mL×3) and brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was passed through a silica pad (NH-silica gel). The filtrate was concentrated under reduced pressure to give the title compound (37.2 g).

Workup

  1. stirringthe mixture was stirred at room temperature for 35 minutes
  2. stirringthe mixture was stirred at room temperature for 90 minutes
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionChloroform (250 mL) and water (80 mL) were added to the resulting residue
  5. customthe organic layer was separated
  6. extractionThe aqueous layer was re-extracted with chloroform (50 mL)
  7. washThe combined organic layers were sequentially washed with a saturated aqueous ammonium chloride solution (60 mL×3) and brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-50bbe1a53a894e27b8e071e1a1a98b2a
Source dataset
uspto-grants-2013_10
Patent number
US08563565B2

Reaction notes

Loading…