1,2-Dichloroethane → 1,1-dimethylethyl (3R)-3-(cyclopentyl methyl)-4-{5-[(dimethylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}-4-oxobutanoate

HRID 1396979Notes

Reaction equation

HRID 1396979 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:8]([N:10]2[CH:14]([C:15](O)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C[CH2:27][N:28](C(C)C)[CH:29](C)C.C(Cl)CCl.CNC>ClCCl.C1COCC1>[CH:1]1([CH2:6][C@@H:7]([C:8]([N:10]2[CH:14]([C:15]([N:28]([CH3:29])[CH3:27])=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 674DimethylamineHCID 81531DiisopropylethylamineHCID 682877191-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid

Product 1

HCID 682880781,1-dimethylethyl (3R)-3-(cyclopentyl methyl)-4-{5-[(dimethylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}-4-oxobutanoateYield 83%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid (353 mg, 1.0 mmol), Hunig's base (0.35 ml, 2.0 mmol), EDC (231 mg, 1.2 mmol) and aza-HOBt (136 mg, 1.0 mmol) in dichloromethane (DCM) (10 ml) was added N-methylmethanamine (1.0 ml, 2.0 mmol), which was in THF. The reaction mixture was stirred at room temperature overnight. The mixture was then washed with water (5 mL), NaHCO3 solution (5 mL×3), and concentrated to provide the crude product which was purified by Combiflash automated silica gel chromatography (0-50% EtOAc in hex) to afford 1,1-dimethylethyl (3R)-3-(cyclopentyl methyl)-4-{5-[(dimethylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}-4-oxobutanoate (315 mg, 0.83 mmol, 83% yield) as a yellow solid. MS: 380 ([M+H]+).

Workup

  1. washThe mixture was then washed with water (5 mL), NaHCO3 solution (5 mL×3)
  2. concentrationconcentrated
  3. customto provide the crude product which
  4. customwas purified by Combiflash automated silica gel chromatography (0-50% EtOAc in hex)

Sources & evidence

ORD record
ord-5af7b5569df34929a520738fb60257b9
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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