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

HRID 1396899

Reaktionsgleichung

Reaktionsgleichung von HRID 1396899
CN1C=CN=C1.[CH:7]1([CH2:12][C@H:13]([CH2:34][N:35]([CH:44]=[O:45])[O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:14]([N:16]2[C@H:20]([C:21](O)=[O:22])[CH2:19][CH2:18][N:17]2[C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])=[O:15])[CH2:11][CH2:10][CH2:9][CH2:8]1.CS(Cl)(=O)=O.[N:51]1[CH:56]=[CH:55][C:54]([NH2:57])=[N:53][CH:52]=1>ClCCl.C(OCC)(=O)C.C(#N)C>[CH:7]1([CH2:12][C@H:13]([CH2:34][N:35]([CH:44]=[O:45])[O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:14]([N:16]2[C@H:20]([C:21]([NH:57][C:54]3[CH:55]=[CH:56][N:51]=[CH:52][N:53]=3)=[O:22])[CH2:19][CH2:18][N:17]2[C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])=[O:15])[CH2:8][CH2:9][CH2:10][CH2:11]1

Komponenten

8

Edukt 4

HCID 13901-MethylimidazoleHCID 31297Methanesulfonyl chlorideHCID 689584-AminopyrimidineHCID 86706346(3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

Produkt 1

HCID 86706355phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[(4-pyrimidinylamino)carbonyl]-1-pyrazolidinecarboxylateAusbeute 92,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

1-Methylimidazole (1.78 mL, 22.3 mmol) was added into a solution of (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (4 g, 7.4 mmol) in dichloromethane (50.8 mL). The resulting solution was cooled to 0° C., and then methanesulfonyl chloride (0.6 mL, 7.8 mmol) was added dropwise at 0° C. To the reaction mixture was added 4-pyrimidinamine (849 mg, 8.9 mmol) and stirring continued for 1.5 h at ambient temperature. The reaction solution was filtered to remove unreacted 4-pyrimidinamine, and the filtrate was concentrated to provide a residue. The residue was dissolved in a mixed solution of ethyl acetate and acetonitrile, and was purified by silica gel chromatography (CombiFlash; Column: 220 g; 0-85% ethyl acetate in hexane; 60 min). The solvent was removed under reduced pressure to yield the desired product, phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[(4-pyrimidinylamino)carbonyl]-1-pyrazolidinecarboxylate (4.22 g, 92% yield). (ES+) m/z 615.2 (MH+).

Aufarbeitung

  1. filtrationThe reaction solution was filtered
  2. customto remove unreacted 4-pyrimidinamine
  3. concentrationthe filtrate was concentrated
  4. customto provide a residue
  5. customwas purified by silica gel chromatography (CombiFlash; Column: 220 g; 0-85% ethyl acetate in hexane; 60 min)
  6. customThe solvent was removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-b5b71bfc49454f3c881f2304b4ca7886
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901119B2

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