(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 → (5S)-1-[(2R)-2-(cyclopentylmethyl)-4-(hydroxyamino)-4-oxobutanoyl]-N-2-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamide

HRID 1396969Notes

Reaction equation

HRID 1396969 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:24][C:25](=[O:34])[NH:26][O:27]C2CCCCO2)[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[N:23]=[CH:22][CH:21]=[CH:20][N:19]=3)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1>C(O)(=O)C.O>[CH:1]1([CH2:6][C@H:7]([CH2:24][C:25]([NH:26][OH:27])=[O:34])[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[N:23]=[CH:22][CH:21]=[CH:20][N:19]=3)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 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-carboxamide

Product 1

HCID 86706395(5S)-1-[(2R)-2-(cyclopentylmethyl)-4-(hydroxyamino)-4-oxobutanoyl]-N-2-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamideYield 36.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

A mixture of (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, 0.17 mmol) in acetic acid (8 mL) and water (2 mL) was stirred at room temperature for 3 days. The solvent was then removed to provide a residue which 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-(hydroxyamino)-4-oxobutanoyl]-N-2-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamide (24 mg, 35% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.15 (br. s., 2H) 1.37-1.94 (m, 9H) 2.41 (br. s., 1H) 2.64 (br. s., 1H) 3.24 (br. s., 2H) 3.52 (br. s., 1H) 3.83 (br. s., 1H) 5.11 (br. s., 1H) 6.99-7.07 (m, 2H) 8.64 (d, J=4.80 Hz, 2H) 9.21 (br. s., 1H) 10.33 (s, 1H).

Workup

  1. customThe solvent was then removed
  2. customto provide a residue which
  3. customwas purified by Gilson HPLC (Sunfire Column 19×50 mm, flowrate 25 mL/min, 10 min, 5-70% MeCN:H2O)

Sources & evidence

ORD record
ord-b177b309049943da968d424012b48867
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

Loading…