Sodium Hydroxide → N,beta,beta-trimethyl-L-phenylalanyl-N1-{(1S,2E)-1-isopropyl-4-[methoxy(methyl)-amino]-3-methyl-4-oxobut-2-enyl}-N1,3-dimethyl-L-valinamide

HRID 133807

Reaktionsgleichung

Reaktionsgleichung von HRID 133807
[CH3:1][NH:2][C@H:3]([C:13]([NH:15][C@H:16]([C:21]([N:23]([C@@H:25]([CH:32]([CH3:34])[CH3:33])/[CH:26]=[C:27](/[C:29]([OH:31])=O)\[CH3:28])[CH3:24])=[O:22])[C:17]([CH3:20])([CH3:19])[CH3:18])=[O:14])[C:4]([CH3:12])([CH3:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl.[CH3:36][NH:37][O:38][CH3:39].[OH-].[Na+]>O1CCCC1.O.[Cl-].[Na+].O>[CH3:1][NH:2][C@H:3]([C:13]([NH:15][C@H:16]([C:21]([N:23]([C@@H:25]([CH:32]([CH3:34])[CH3:33])/[CH:26]=[C:27](\[CH3:28])/[C:29]([N:37]([O:38][CH3:39])[CH3:36])=[O:31])[CH3:24])=[O:22])[C:17]([CH3:18])([CH3:20])[CH3:19])=[O:14])[C:4]([CH3:12])([CH3:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Komponenten

7

Edukt 3

HCID 14798Sodium Hydroxide2×HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 6918637N,beta,beta-Trimethyl-L-phenylalanyl-N-((1S,2E)-3-carboxy-1-(1-methylethyl)-2-buten-1-yl)-N,3-dimethyl-L-valinamide

Produkt 1

HCID 11656496N,beta,beta-trimethyl-L-phenylalanyl-N1-{(1S,2E)-1-isopropyl-4-[methoxy(methyl)-amino]-3-methyl-4-oxobut-2-enyl}-N1,3-dimethyl-L-valinamideAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

A solution of N,β,β-trimethyl-L-phenylalanyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide (473 mg, 1 mmol, WO 99/32509) in tetrahydrofuran (2 mL) is added a solution of N,O-dimethylhydroxylamine hydrochloride (166 mg, 1.7 mmol) in water (2 mL), adjusting the reaction mixture to pH 4.5 by adding dropwise 1.0 N sodium hydroxide solution. To this is added dropwise a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimine hydrochloride (479 mg, 2.5 mmol) in water (7 mL) over a period of 7 min, maintaining pH 4.5 by using 1.0 N sodium hydroxide solution. The reaction mixture is stirred at room temperature for 2.5 h, adjusting the pH to 6-7. To this is added brine (10 mL) and extracted with dichloromethane. The combined organic layers are washed with brine, dried (Na2SO4), filtered and concentrated to give 491 mg (95%) of the title compound as a white solid. HRMS (ESI) calcd for C29H48N4O4 (M+H+) 517.3748, found 517.3750.

Aufarbeitung

  1. temperaturemaintaining pH 4.5
  2. extractionextracted with dichloromethane
  3. washThe combined organic layers are washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-47f1c2a29b7147a8966671c671391628
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07390910B2

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