1-Methylimidazole → Phenylmethyl (3S)-3-{[(6-chloro-2-pyridinyl)amino]carbonyl}-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-pyrazolidinecarboxylate

HRID 1396872

Reaktionsgleichung

Reaktionsgleichung von HRID 1396872
[CH:1]1([CH2:6][C@H:7]([CH2:28][N:29]([CH:38]=[O:39])[O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:8]([N:10]2[CH:14]([C:15]([OH:17])=O)[CH2:13][CH2:12][N:11]2[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.CN1C=CN=C1.S(Cl)(C)(=O)=O.[NH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[C:54]([Cl:58])[N:53]=1>C1(C[C@H](CN(C=O)OCC2C=CC=CC=2)C(N2[C@H](C(O)=O)CCN2C(OCC2C=CC=CC=2)=O)=O)CCCC1.ClCCl>[Cl:58][C:54]1[N:53]=[C:52]([NH:51][C:15]([C@@H:14]2[CH2:13][CH2:12][N:11]([C:18]([O:20][CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)=[O:19])[N:10]2[C:8](=[O:9])[C@@H:7]([CH2:28][N:29]([CH:38]=[O:39])[O:30][CH2:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[O:17])[CH:57]=[CH:56][CH:55]=1

Komponenten

7

Edukt 4

HCID 13901-MethylimidazoleHCID 31297Methanesulfonyl chlorideHCID 2062462-Amino-6-chloropyridineHCID 86706341HCID 86706341, Verbindung

Produkt 1

HCID 86706347Phenylmethyl (3S)-3-{[(6-chloro-2-pyridinyl)amino]carbonyl}-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-pyrazolidinecarboxylateAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 86706346(3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acidLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidine carboxylic acid (as a mixture of diastereomers enriched in (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid) (300 mg, 0.558 mmol) in dichloromethane (5 ml) was added 1-methylimidazole (133 μl, 1.674 mmol) and cooled to 0° C. Mesyl chloride (56 μL, 0.725 mmol) was added dropwise at 0° C. and stirred for 1 hr at rt. The mixture was then treated with 2-amino-6-chloropyridine (86 mg, 0.67 mmol). The solvent mixture was removed. The residue was diluted with MeOH and purified by reverse-phase HPLC to afford 268 mg (0.413 mmol, 74%) of the title compound. LC/MS: (M+H)+: 648.3.

Aufarbeitung

  1. customThe solvent mixture was removed
  2. additionThe residue was diluted with MeOH
  3. custompurified by reverse-phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-b9f4b97b6fe44fa2b9aa5606260cc5d4
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901119B2

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