Pyrazole → HCID 59543614, compound

HRID 1697702Notes

Reaction equation

HRID 1697702 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:12]([C:14]1([NH:17][C:18]([C@@H:20]2[CH2:24][C@@H:23]([S:25]([C:28]3[CH:33]=[CH:32][C:31](F)=[CH:30][C:29]=3[C:35]([F:38])([F:37])[F:36])(=[O:27])=[O:26])[CH2:22][N:21]2[C:39]2[N:40]([CH:45]3[CH2:48][CH2:47][CH2:46]3)[N:41]=[C:42]([CH3:44])[CH:43]=2)=[O:19])[CH2:16][CH2:15]1)#[N:13].C(OC(C)=O)(C)C>CC(N(C)C)=O>[C:12]([C:14]1([NH:17][C:18]([C@@H:20]2[CH2:24][C@@H:23]([S:25]([C:28]3[CH:33]=[CH:32][C:31]([N:1]4[CH:5]=[CH:4][CH:3]=[N:2]4)=[CH:30][C:29]=3[C:35]([F:36])([F:38])[F:37])(=[O:26])=[O:27])[CH2:22][N:21]2[C:39]2[N:40]([CH:45]3[CH2:48][CH2:47][CH2:46]3)[N:41]=[C:42]([CH3:44])[CH:43]=2)=[O:19])[CH2:16][CH2:15]1)#[N:13]

Participants

6

Reactant 4

HCID 1048PyrazoleHCID 7915Isopropyl AcetateHCID 10796Cesium carbonateHCID 66770568HCID 66770568, compound

Product 1

HCID 59543614HCID 59543614, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Pyrazole (5 mg, 67 umol; CAS Reg. No. 288-11-9) and cesium carbonate (18 mg, 56 umol) were added to a solution of (2S,4R)-1-(2-cyclobutyl-5-methyl-2H-pyrazol-3-yl)-4-(4-fluoro-2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide (30 mg, 56 umol; example 388 g) in DMA (0.9 ml) under an argon atmosphere. The mixture was heated for 48 h to 90° C. and for additional 4 h to 120° C. in a shaking reactor. Ice water/brine 1/1 and iPrOAc were added and the layers were separated. The aqueous layer was extracted one more time with iPrOAc. The combined extracts were washed with ice water/brine 1/1, dried over sodium sulfate and filtered. The solvent was removed under reduced pressure to give a brown oil which was purified by preparative HPLC to give the title compound (6.5 mg, 11 umol; 20%) as colorless oil. MS (ESI): m/z=588.4 [M+H]+.

Workup

  1. temperatureThe mixture was heated for 48 h to 90° C. and for additional 4 h to 120° C. in a shaking reactor
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted one more time with iPrOAc
  4. washThe combined extracts were washed with ice water/brine 1/1
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed under reduced pressure
  8. customto give a brown oil which
  9. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-e05c7799e6ae416d8f3bb5e8ecb46ee6
Source dataset
uspto-grants-2012_04
Patent number
US08163793B2

Reaction notes

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