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 1396972Notes

Reaction equation

HRID 1396972 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.CN1CCOCC1.Cl.[C:38]1([CH2:44][O:45][NH2:46])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(Cl)CCl.N1C2C(=NC=CC=2)N(O)N=1>ClCCl>[CH:1]1([CH2:6][C@H:7]([CH2:8][C:9](=[O:11])[NH:46][O:45][CH2:44][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=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 102312Benzyloxyamine hydrochlorideHCID 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 39.3%

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 (314 mg, 0.79 mmol) in dichloromethane (DCM) (10 mL) was added N-methylmorpholine (0.22 mL, 2.04 mmol), O-(phenylmethyl)hydroxylamine hydrochloride (188 mg, 1.18 mmol), EDC (181 mg, 0.94 mmol) and 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (107 mg, 0.79 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature and was stirred overnight. The reaction mixture was then washed with water (5 mL) and NaHCO3 solution (5 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-(6-ethyl-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (157 mg, 39% yield). MS: 506 ([M+H]+).

Workup

  1. washThe reaction mixture was then washed with water (5 mL) and NaHCO3 solution (5 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-527af3f0afda4deba8c23502bede43b5
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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