HCID 86706349, compound → HCID 66547913, compound

HRID 1396877Notes

Reaction equation

HRID 1396877 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:35][N:36]([CH:45]=[O:46])[O:37]CC2C=CC=CC=2)[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][N:19]=3)=[O:16])[CH2:13][CH2:12][N:11]2C(OCC2C=CC=CC=2)=O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1>CO.[OH-].[OH-].[Pd+2]>[CH:1]1([CH2:6][C@H:7]([CH2:35][N:36]([CH:45]=[O:46])[OH:37])[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][N:19]=3)=[O:16])[CH2:13][CH2:12][NH:11]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 1

HCID 86706349HCID 86706349, compound

Product 1

HCID 66547913HCID 66547913, compoundYield 75.2%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To a solution of phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-{[(5-methyl-2-pyridinyl)amino]carbonyl}-1-pyrazolidinecarboxylate (combined from Part A, Batches 1 and 2, 142 mg, 0.226 mmol) in methanol (6 ml) was added 20% palladium hydroxide on carbon (70 mg, 0.226 mmol). The mixture was hydrogenated under balloon pressure for 1 h 30 min. and then filtered. The mixture was purified by reverse-phase HPLC to yield (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-methyl-2-pyridinyl)-3-pyrazolidine carboxamide (68 mg, 0.170 mmol, 75% yield). LC/MS: (M+H)+: 404.0. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.06-1.26 (m, 2H) 1.35-1.48 (m, 1H) 1.48-1.69 (m, 4H) 1.69-1.99 (m, 4H) 2.17-2.31 (m, 3H) 2.45-2.64 (m, 1H) 2.80-3.01 (m, 1H) 3.16-3.31 (m, 1H) 3.51 (dd, J=14.02, 4.42 Hz, 1H) 3.66-3.84 (m, 2H) 3.95 (dt, J=9.35, 4.67 Hz, 1H) 4.70 (td, J=7.96, 4.04 Hz, 1H) 7.61 (dd, J=8.08, 2.02 Hz, 1H) 7.88 (s, 1H) 7.98 (d, J=8.34 Hz, 1H) 8.13 (d, J=2.27 Hz, 1H).

Workup

  1. filtrationfiltered
  2. customThe mixture was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-199fa890aeb745a08a90bdfcf372b1d6
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

Loading…