phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({2-[(3S)-3-(dimethylamino)-1-pyrrolidinyl]-4-pyrimidinyl}amino)carbonyl]-1-pyrazolidinecarboxylate → HCID 66546321, compound

HRID 1396912Notes

Reaction equation

HRID 1396912 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]=[CH:22][N:21]=[C:20]([N:24]4[CH2:28][CH2:27][C@H:26]([N:29]([CH3:31])[CH3:30])[CH2:25]4)[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>[OH-].[OH-].[Pd+2].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]=[CH:22][N:21]=[C:20]([N:24]4[CH2:28][CH2:27][C@H:26]([N:29]([CH3:31])[CH3:30])[CH2:25]4)[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 86706356phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({2-[(3S)-3-(dimethylamino)-1-pyrrolidinyl]-4-pyrimidinyl}amino)carbonyl]-1-pyrazolidinecarboxylate

Product 1

HCID 66546321HCID 66546321, compoundYield 71.2%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

A mixture of phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({2-[(3S)-3-(dimethylamino)-1-pyrrolidinyl]-4-pyrimidinyl}amino)carbonyl]-1-pyrazolidinecarboxylate (91 mg, 0.125 mmol) and Pearlman's catalyst (17.58 mg, 0.025 mmol) in methanol (7.4 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-{2-[(3S)-3-(dimethylamino)-1-pyrrolidinyl]-4-pyrimidinyl}-3-pyrazolidinecarboxamide (45 mg, 0.089 mmol, 71% yield). MS (ES+) m/z 503.1 (MH+). 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.05-1.23 (m, 2H) 1.33-1.45 (m, 1H) 1.45-1.68 (m, 4H) 1.69-1.96 (m, 5H) 2.12-2.31 (m, 2H) 2.34 (s, 6H) 2.42-2.57 (m, 1H) 2.83-2.96 (m, 2H) 3.18-3.30 (m, 2H) 3.40-3.53 (m, 2H) 3.65-3.83 (m, 2H) 3.84-3.99 (m, 2H) 4.68 (q, J=7.16 Hz, 1H) 7.34 (d, J=5.56 Hz, 1H) 7.85 (s, 0.7H) 8.16 (d, J=5.81 Hz, 1H) 8.25 (s, 0.3H)

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-0a89b256414a4ecc8f62d88885a0a34c
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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