Hydrogen chloride-ethyl acetate → HCID 178516171, compound

HRID 2192954Notes

Reaction equation

HRID 2192954 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:32][C@H:33]3[CH2:37][CH2:36][C:35](=[O:38])[CH2:34]3)[C:17]([NH:19][C:20]3[CH:24]=[CH:23][N:22](C(OC(C)(C)C)=O)[N:21]=3)=[O:18])[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH2:3][CH2:2]1.Cl.C(OCC)(=O)C>C(OCC)(=O)C>[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:32][C@H:33]3[CH2:37][CH2:36][C:35](=[O:38])[CH2:34]3)[C:17]([NH:19][C:20]3[CH:24]=[CH:23][NH:22][N:21]=3)=[O:18])[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:11])=[O:12])[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 68671064tert-butyl 3-({(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoyl}amino)-1H-pyrazole-1-carboxylate

Product 1

HCID 178516171HCID 178516171, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 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. customThe solvent was evaporated under reduced pressure, ethyl acetate (20 mL) and saturated aqueous sodium bicarbonate (20 mL)
  3. additionwere added
  4. washthe organic layer was washed with saturated brine (20 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was then purified by silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-0d5dbcbed1d34005ade70b48645a20a8
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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