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

HRID 1396900Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1396900
[CH:1]1([CH2:6][C@H:7]([CH2:34][N:35]([CH:44]=[O:45])[O:36]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]=[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>[OH-].[OH-].[Pd+2].CO>[CH:1]1([CH2:6][C@H:7]([CH2:34][N:35]([CH:44]=[O:45])[OH:36])[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][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

Komponenten

4

Edukt 1

HCID 86706355phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[(4-pyrimidinylamino)carbonyl]-1-pyrazolidinecarboxylate

Produkt 1

HCID 66548431(3S)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-4-pyrimidinyl-3-pyrazolidinecarboxamideAusbeute 67,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9942167Palladium hydroxideKatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

A mixture of phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[(4-pyrimidinylamino)carbonyl]-1-pyrazolidinecarboxylate (4.22 g, 6.87 mmol) and Pearlman's catalyst (964 mg, 1.37 mmol) in methanol (381 mL) was degassed and placed under 1 atm of H2 at 25° C. After 2 hrs, the reaction mixture was filtered and concentrated to give a crude residue which was purified by RP-HPLC to provide (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-4-pyrimidinyl-3-pyrazolidinecarboxamide as a foamy solid (1.8 g, 67% yield). The material was dissolved and evaporated from acetonitrile (2×5 mL) to provide a white solid. MS (ES+) m/z 391.2 (MH+). 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.06-1.23 (m, 2H) 1.34-1.47 (m, 1H) 1.47-1.67 (m, 4H) 1.69-1.97 (m, 4H) 2.15-2.29 (m, 1H) 2.45-2.60 (m, 1H) 2.85-2.99 (m, 1H) 3.20-3.28 (m, 1H) 3.49 (dd, J=13.89, 4.55 Hz, 1H) 3.59-3.85 (m, 1H) 3.94 (dt, J=9.41, 4.77 Hz, 1H) 4.64-4.74 (m, 1H) 7.86 (s, 0.7H) 8.17 (dd, J=6.06, 1.26 Hz, 1H) 8.25 (s, 0.3H) 8.60 (d, J=6.06 Hz, 1H) 8.82 (s, 1H).

Aufarbeitung

  1. customwas degassed
  2. customplaced under 1 atm of H2 at 25° C
  3. filtrationthe reaction mixture was filtered
  4. concentrationconcentrated
  5. customto give a crude residue which
  6. customwas purified by RP-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-aa8b3255d48f49a2be110958719cab04
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901119B2

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