Hydrochloric Acid → tert-butyl 3-({(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoyl}amino)-1H-pyrazole-1-carboxylate

HRID 2192953Notes

Reaction equation

HRID 2192953 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:20][C@H:21]3[CH2:25][CH2:24][C:23](=[O:26])[CH2:22]3)[C:17](O)=[O:18])[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:33][C:34]1[CH:38]=[CH:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[N:35]=1.Cl>ClCCl.C(OCC)(=O)C.N1C=CC=CC=1.CN(C=O)C>[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:20][C@H:21]3[CH2:25][CH2:24][C:23](=[O:26])[CH2:22]3)[C:17]([NH:33][C:34]3[CH:38]=[CH:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[N:35]=3)=[O:18])[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH2:2][CH2:3]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 51358380tert-Butyl 3-amino-1H-pyrazole-1-carboxylateHCID 59570882(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoic acid

Product 1

HCID 68671064tert-butyl 3-({(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoyl}amino)-1H-pyrazole-1-carboxylateYield 85.6%

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propionic acid (160 mg) in dichloromethane (5 mL) were added oxalyl chloride (0.04 mL) and a drop of DMF under ice-cooling, followed by stirring for 1 hour under ice-cooling. To the reaction mixture were sequentially added pyridine (0.04 mL) and tert-butyl 3-amino-1H-pyrazole-1-carboxylate (90 mg), followed by stirring at room temperature overnight. To the reaction mixture were added ethyl acetate (30 mL) and 1 M hydrochloric acid (30 mL), and the organic layer was sequentially washed with saturated aqueous sodium bicarbonate (30 mL) and saturated brine (30 mL). After drying over anhydrous magnesium sulfate, the solvent was then evaporated under reduced pressure to obtain tert-butyl 3-({(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoyl}amino)-1H-pyrazole-1-carboxylate (197 mg) as a pale yellow amorphous substance. To a solution of tert-butyl 3-({(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoyl}amino)-1H-pyrazole-1-carboxylate (190 mg) in ethyl acetate (5 mL) was added 4 M hydrogen chloride/ethyl acetate (5 mL) under ice-cooling, followed by stirring at room temperature overnight. The solvent was evaporated under reduced pressure, ethyl acetate (20 mL) and saturated aqueous sodium bicarbonate (20 mL) were added thereto, and the organic layer was washed with saturated brine (20 mL) and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was then purified by silica gel column chromatography (ethyl acetate) to obtain (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]-N-1H-pyrazol-3-yl propanamide (62 mg) as a colorless amorphous substance.

Workup

  1. temperaturecooling
  2. stirringby stirring at room temperature overnight
  3. washthe organic layer was sequentially washed with saturated aqueous sodium bicarbonate (30 mL) and saturated brine (30 mL)
  4. dry with materialAfter drying over anhydrous magnesium sulfate
  5. customthe solvent was then evaporated under reduced pressure

Sources & evidence

ORD record
ord-5746e941f32d44d985c32869b4051f6a
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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