1,2-Dichloroethane → (5S)-1-{(2R)-2-(cyclopentylmethyl)-4-oxo-4-[(tetrahydro-2H-pyran-2-yloxy)amino]butanoyl}-N-2-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamide

HRID 1396968Notes

Reaction equation

HRID 1396968 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[N:26]=[CH:25][CH:24]=[CH:23][N:22]=3)=[O:19])[CH2:16][CH:15]=[N:14]2)[CH2:8][C:9]([OH:11])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.[O:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH:36]1[O:41][NH2:42].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:42][O:41][CH:36]2[CH2:37][CH2:38][CH2:39][CH2:40][O:35]2)[C:12]([N:13]2[C@H:17]([C:18]([NH:20][C:21]3[N:22]=[CH:23][CH:24]=[CH:25][N:26]=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 181649HOAtHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 68287994(3R)-3-(Cyclopentylmethyl)-4-oxo-4-{5-[(2-pyrimidinylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoic acid

Product 1

HCID 86706394(5S)-1-{(2R)-2-(cyclopentylmethyl)-4-oxo-4-[(tetrahydro-2H-pyran-2-yloxy)amino]butanoyl}-N-2-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamideYield 34.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3R)-3-(cyclopentylmethyl)-4-oxo-4-{5-[(2-pyrimidinylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoic acid (183 mg, 0.49 mmol) in dichloromethane (DCM) (10 mL) was added N-methylmorpholine (0.14 mL, 1.27 mmol), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (69 mg, 0.59 mmol), EDC (112 mg, 0.59 mmol) and 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (67 mg, 0.49 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature and was stirred for 2 hours. 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, 5-70% MeCN:H2O) to afford (5S)-1-{(2R)-2-(cyclopentylmethyl)-4-oxo-4-[(tetrahydro-2H-pyran-2-yloxy)amino]butanoyl}-N-2-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamide (80 mg, 34% yield). MS: 473 ([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, 5-70% MeCN:H2O)

Sources & evidence

ORD record
ord-c0b265d5c98d497399fbc4d3b8cc361d
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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