phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({6-[(2R)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}amino)carbonyl]-1-pyrazolidinecarboxylate → (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-{6-[(2R)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}-3-pyrazolidinecarboxamide

HRID 1396921Notes

Reaction equation

HRID 1396921 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:42][N:43]([CH:52]=[O:53])[O:44]CC2C=CC=CC=2)[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[C:22]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][C@H:25]4[CH3:31])[N:21]=[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>[CH:1]1([CH2:6][C@H:7]([CH2:42][N:43]([CH:52]=[O:53])[OH:44])[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[C:22]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][C@H:25]4[CH3:31])[N:21]=[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

3

Reactant 1

HCID 86706363phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({6-[(2R)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}amino)carbonyl]-1-pyrazolidinecarboxylate

Product 1

HCID 86706364(3S)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-{6-[(2R)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}-3-pyrazolidinecarboxamideYield 85%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({6-[(2R)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}amino)carbonyl]-1-pyrazolidinecarboxylate (71 mg, 0.098 mmol) and Perrlman's catalyst (13.72 mg, 0.020 mmol) in methanol (5.4 ml) was degassed and placed under 1 atm of H2 at ambient temperature. After 2 hrs, the reaction mixture was filtered and concentrated to give a residue which was purified by RP-HPLC to give (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-{6-[(2R)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}-3-pyrazolidinecarboxamide (42 mg, 0.083 mmol, 85% yield). MS (ES+) m/z 503.2 (MH+). 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.05-1.22 (m, 2H) 1.27 (d, J=6.82 Hz, 3H) 1.36-1.45 (m, 1H) 1.46-1.67 (m, 4H) 1.69-1.95 (m, 4H) 2.03 (td, J=11.94, 3.41 Hz, 1H) 2.22 (dd, J=11.62, 4.04 Hz, 2H) 2.26-2.34 (m, 3H) 2.41-2.56 (m, 1H) 2.81 (d, J=11.62 Hz, 1H) 2.85-2.98 (m, 2H) 3.10-3.27 (m, 2H) 3.49 (dd, J=14.02, 4.42 Hz, 1H) 3.59-3.84 (m, 1H) 3.84-3.99 (m, 1H) 4.17 (d, J=13.14 Hz, 1H) 4.53 (br. s., 1H) 4.61-4.72 (m, 1H) 7.41 (s, 1H) 7.86 (s, 0.7H) 8.24 (s, 1.3H).

Workup

  1. customwas degassed
  2. customplaced under 1 atm of H2 at ambient temperature
  3. filtrationthe reaction mixture was filtered
  4. concentrationconcentrated
  5. customto give a residue which
  6. customwas purified by RP-HPLC

Sources & evidence

ORD record
ord-d0ff44cd68674ec9a35690435b74d1ec
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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