Ethyl Acetate → (S)-2-[(2-Carbamoyl-2-methyl-propylcarbamoyl)-methyl]-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1963072Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1963072
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[N:24]3[C:19]([CH:20]=[CH:21][CH:22]=[CH:23]3)=[C:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:17]=2[CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[CH3:39])=[O:15])[CH2:10][C@@H:9]1[CH2:40][C:41](O)=[O:42])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:44][CH2:45][C:46]([CH3:51])([CH3:50])[C:47]([NH2:49])=[O:48].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CC(=O)OCC>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[N:24]3[C:19]([CH:20]=[CH:21][CH:22]=[CH:23]3)=[C:18]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:17]=2[CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[CH3:39])=[O:15])[CH2:10][C@@H:9]1[CH2:40][C:41](=[O:42])[NH:44][CH2:45][C:46]([C:47](=[O:48])[NH2:49])([CH3:51])[CH3:50])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Komponenten

6

Edukt 4

HCID 8857Ethyl AcetateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 111593153-Amino-2,2-dimethylpropanamideHCID 70663959{(S)-1-tert-Butoxycarbonyl-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazin-2-yl}-acetic acid

Produkt 1

HCID 67773127(S)-2-[(2-Carbamoyl-2-methyl-propylcarbamoyl)-methyl]-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazine-1-carboxylic acid tert-butyl esterAusbeute 91,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

The compound of step 5 (0.176 g, 0.30 mmol) was dissolved in 2.5 ml of anhydrous DCM at 0° C. 3-Amino-2,2-dimethyl-propionamide (0.044 g, 0.38 mmol), EDIA (0.13 ml, 0.75 mmol) and TBTU (0.120 g, 0.38 mmol) were added and the solution was stirred at room temperature for 60 h. EA (15 ml) was then added and the solution was washed with water, 1 N hydrochloric acid, a saturated solution of sodium hydrogencarbonate and brine. The organic phase was dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica gel (EA/MOH, 100:0, then 97:5, then 95:5) to give 0.188 g of the title compound as a greenish-brown wax.

Aufarbeitung

  1. washthe solution was washed with water, 1 N hydrochloric acid
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated under reduced pressure
  5. customThe residue was purified by chromatography on silica gel (EA/MOH, 100:0

Quellen und Nachweise

ORD-Eintrag
ord-efc0894f6a164684aa8ce60793ac228b
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415336B2

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