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

HRID 1396981Notes

Reaction equation

HRID 1396981 reaction equation
[CH:1]1([CH2:6][C@@H:7]([C:12]([N:14]2[CH:18]([C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH2:17][CH:16]=[N:15]2)=[O:13])[CH2:8][C:9]([OH:11])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:24]1([CH2:30][O:31][NH2:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(Cl)CCl.CN1CCOCC1.N1C2C(=NC=CC=2)N(O)N=1>ClCCl>[CH:1]1([CH2:6][C@H:7]([CH2:8][C:9](=[O:11])[NH:32][O:31][CH2:30][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:12]([N:14]2[C@H:18]([C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH2:17][CH:16]=[N:15]2)=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 102313O-BenzylhydroxylamineHCID 181649HOAtHCID 68287954(3R)-3-(cyclopentylmethyl)-4-{5-[(dimethylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}-4-oxobutanoic acid

Product 1

HCID 86706401(5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N,N-dimethyl-4,5-dihydro-1H-pyrazole-5-carboxamideYield 33.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3R)-3-(cyclopentylmethyl)-4-{5-[(dimethylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}-4-oxobutanoic acid (269 mg, 0.83 mmol) in dichloromethane (DCM) (10 ml) was added O-(phenylmethyl)hydroxylamine (133 mg, 1.08 mmol), EDC (191 mg, 1.0 mmol), 4-methylmorpholine (0.24 ml, 2.16 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (113 mg, 0.83 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature and was stirred for 5 hours. The reaction mixture was then washed with water (15 mL) and NaHCO3 solution (15 mL×3), and concentrated to provide the crude product as a mixture of diastereomers. This mixture was purified by Gilson HPLC (Sunfire Column 19×50 mm, flowrate 25 mL/min, 10 min, 5-65% MeCN:H2O) to afford (5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N,N-dimethyl-4,5-dihydro-1H-pyrazole-5-carboxamide (120 mg, 33% yield). MS: 429 ([M+H]+).

Workup

  1. washThe reaction mixture was then washed with water (15 mL) and NaHCO3 solution (15 mL×3)
  2. concentrationconcentrated
  3. customto provide the crude product
  4. additionas a mixture of diastereomers
  5. customThis mixture was purified by Gilson HPLC (Sunfire Column 19×50 mm, flowrate 25 mL/min, 10 min, 5-65% MeCN:H2O)

Sources & evidence

ORD record
ord-a9f91f6ab0c24139b8deb30288dc690b
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

Loading…