1,2-Dichloroethane → (5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N-phenyl-4,5-dihydro-1H-pyrazole-5-carboxamide

HRID 1396989Notes

Reaction equation

HRID 1396989 reaction equation
[CH:1]1([CH2:6][C@@H:7]([C:12](=[O:27])[N:13]2[CH:17]([C:18]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:19])[CH2:16][CH:15]=[N:14]2)[CH2:8][C:9](O)=[O:10])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:28]1([CH2:34][O:35][NH2:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.CN1CCOCC1.N1C2C(=NC=CC=2)N(O)N=1.C(Cl)CCl>ClCCl>[CH:1]1([CH2:6][C@H:7]([CH2:8][C:9](=[O:10])[NH:36][O:35][CH2:34][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:12]([N:13]2[C@H:17]([C:18]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:19])[CH2:16][CH:15]=[N:14]2)=[O:27])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 102313O-BenzylhydroxylamineHCID 181649HOAtHCID 68287943(3R)-3-(cyclopentylmethyl)-4-oxo-4-{5-[(phenylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoic acid

Product 1

HCID 86706405(5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N-phenyl-4,5-dihydro-1H-pyrazole-5-carboxamideYield 25.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3R)-3-(cyclopentylmethyl)-4-oxo-4-{5-[(phenylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoic acid (336 mg, 0.90 mmol) in dichloromethane (DCM) (10 ml) was added O-(phenylmethyl)hydroxylamine (167 mg, 1.36 mmol), 4-methylmorpholine (0.26 ml, 2.35 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (123 mg, 0.90 mmol), and EDC (208 mg, 1.09 mmol) at 0° C. The reaction was left to warm to room temperature and stirred overnight. The reaction was washed with water (15 mL) and NaHCO3 solution (15 mL×3), and then concentrated to give the crude product as a mixture of diastereomers, which was purified by Gilson HPLC (Sunfire Column 19×50 mm, flowrate 25 mL/min, 10 min, 5-65% MeCN:H2) to afford (5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N-phenyl-4,5-dihydro-1H-pyrazole-5-carboxamide (110 mg, 25% yield). MS: 477 ([M+H]).

Workup

  1. waitThe reaction was left
  2. washThe reaction was washed with water (15 mL) and NaHCO3 solution (15 mL×3)
  3. concentrationconcentrated
  4. customto give the crude product
  5. additionas a mixture of diastereomers, which
  6. customwas purified by Gilson HPLC (Sunfire Column 19×50 mm, flowrate 25 mL/min, 10 min, 5-65% MeCN:H2)

Sources & evidence

ORD record
ord-e9800271eab14e13b5a751e57dd65785
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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