4-Methylmorpholine → HCID 178523395, Verbindung

HRID 1396881

Reaktionsgleichung

Reaktionsgleichung von HRID 1396881
[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[C@H:14]([C:15](O)=[O:16])[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.[NH:40]1[C:44]2[CH:45]=[CH:46][C:47]([NH2:49])=[CH:48][C:43]=2[N:42]=[N:41]1.CN1CCOCC1>C(#N)C>[NH:40]1[C:44]2[CH:45]=[CH:46][C:47]([NH:49][C:15]([C@@H:14]3[CH2:13][CH2:12][N:11]([C:18]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:19])[N:10]3[C:8](=[O:9])[C@@H:7]([CH2:28][N:29]([CH:38]=[O:39])[O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:6][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[O:16])=[CH:48][C:43]=2[N:42]=[N:41]1

Komponenten

5

Edukt 3

HCID 79724-MethylmorpholineHCID 86706346(3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acidHCID 178507366HCID 178507366, Verbindung

Produkt 1

HCID 178523395HCID 178523395, VerbindungAusbeute 69,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a solution of (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidine carboxylic acid (103.1 mg, 0.192 mmol), 1H-1,2,3-benzotriazol-5-amine (56.6 mg, 0.422 mmol), and N-methylmorpholine (46.4 μl, 0.422 mmol) in acetonitrile (1.87 ml) was added DMTMM tetrafluoroborate (69.2 mg, 0.211 mmol). The solution was stirred for 3 days, and then concentrated in vacuo. The residue was dissolved in EtOAc (100 mL), and washed with 1 N aq. HCl (50 mL), followed by 5% aq. NaHCO3. The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by Gilson RPLC (20% to 90% MeCN in water, 8 min gradient), and the desired fractions were combined, and concentrated in vacuo. The residue was azeotroped with MeOH (2×30 mL) to give phenylmethyl (3S)-3-[(1H-1,2,3-benzotriazol-5-ylamino)carbonyl]-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-pyrazolidinecarboxylate (87.2 mg, 0.133 mmol, 69.6% yield) as a light yellow oil. LC/MS: (M+H)+: 654.5. Reference for DMTMM tetrafluoroborate: Raw, S. A. Tetrahedron Lett. 2009, 50, 946.

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc (100 mL)
  3. washwashed with 1 N aq. HCl (50 mL)
  4. dry with materialThe organic phase was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by Gilson RPLC (20% to 90% MeCN in water, 8 min gradient)
  8. concentrationconcentrated in vacuo
  9. customThe residue was azeotroped with MeOH (2×30 mL)

Quellen und Nachweise

ORD-Eintrag
ord-361a8df678bd4d90a46b633aed4bf491
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901119B2

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