1,2-Dichloroethane → (5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N-(6-ethyl-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide

HRID 1396993Notes

Reaction equation

HRID 1396993 reaction equation
[CH:1]1([CH2:6][C@@H:7]([C:12]([N:14]2[CH:18]([C:19]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][CH3:29])[N:23]=3)=[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:30]1([CH2:36][O:37][NH2:38])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=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:11])[NH:38][O:37][CH2:36][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:12]([N:14]2[C@H:18]([C:19]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][CH3:29])[N:23]=3)=[O:20])[CH2:17][CH:16]=[N:15]2)=[O:13])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 102313O-BenzylhydroxylamineHCID 181649HOAtHCID 68287965(3R)-3-(cyclopentyl methyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid

Product 1

HCID 86706396(5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N-(6-ethyl-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamideYield 29.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid (323 mg, 0.81 mmol) in dichloromethane (DCM) (10 ml) was added O-(phenylmethyl)hydroxylamine (129 mg, 1.05 mmol), 4-methylmorpholine (0.23 ml, 2.1 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (110 mg, 0.81 mmol), and EDC (186 mg, 0.97 mmol) at 0° C. The reaction was left to warm to room temperature and stirred overnight. The reaction was then washed with water (15 mL) and NaHCO3 solution (15 mL×3), then concentrated to provide 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: H2O) to afford (5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N-(6-ethyl-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (119 mg, 29% yield). MS: 506 ([M+H]+).

Workup

  1. waitThe reaction was left
  2. washThe reaction was then washed with water (15 mL) and NaHCO3 solution (15 mL×3)
  3. concentrationconcentrated
  4. customto provide 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: H2O)

Sources & evidence

ORD record
ord-facae5ae938b4090b1db0ed6ce5ade63
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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