Triethylamine → N-{(1S)-1-[(S)-(3-fluorophenyl)-{[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy}methyl}-3-methyl-butyl}-2-methoxyacetamide

HRID 13130

Reaktionsgleichung

Reaktionsgleichung von HRID 13130
[F:1][C:2]1[CH:3]=[C:4]([CH:8]([O:15][C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[N:20]=[CH:19]3)[C@H:9]([CH2:11][CH:12]([CH3:14])[CH3:13])[NH2:10])[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[CH3:39][O:40][CH2:41][C:42](Cl)=[O:43]>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C@H:8]([O:15][C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[N:20]=[CH:19]3)[C@@H:9]([NH:10][C:42](=[O:43])[CH2:41][O:40][CH3:39])[CH2:11][CH:12]([CH3:14])[CH3:13])[CH:5]=[CH:6][CH:7]=1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 96623Methoxyacetyl chlorideHCID 66812773(alphaS)-3-Fluoro-beta-[[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy]-alpha-(2-methylpropyl)benzeneethanamine

Produkt 1

HCID 66812792N-{(1S)-1-[(S)-(3-fluorophenyl)-{[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy}methyl}-3-methyl-butyl}-2-methoxyacetamideAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

(αS)-3-Fluoro-β-[[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy]-α-(2-methylpropyl)benzeneethanamine (76.4 mg, 0.18 mmol) is dissolved in 7 mL dichloromethane. Triethylamine (0.06 mL, 0.44 mmol) and 2-methoxyacetyl chloride (0.02 mL, 0.22 mmol) are added. After stirring overnight the reaction mixture is diluted with dichloromethane, washed with water and brine and dried over Na2SO4. After filtration the solvent is evaporated and the residue is purified by chromatography (silicagel, eluents: ethylacetate/hexane). The obtained mixture of the two stereoisomers is separated by HPLC (Chiralpak AD-H 5 μm, eluents: hexane/ethanol) yielding 3.7 mg (10.2%) of the title stereoisomer and 24.7 mg (68%) of the stereoisomer N-{(1S)-1-[(S)-(3-fluorophenyl)-{[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy}methyl}-3-methyl-butyl}-2-methoxyacetamide.

Aufarbeitung

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. filtrationAfter filtration the solvent
  4. customis evaporated
  5. customthe residue is purified by chromatography (silicagel, eluents: ethylacetate/hexane)
  6. additionThe obtained mixture of the two stereoisomers
  7. customis separated by HPLC (Chiralpak AD-H 5 μm, eluents: hexane/ethanol)

Quellen und Nachweise

ORD-Eintrag
ord-ad49fd55b692495fa7edb0d6eaadbea5
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07728030B2

Verknüpfte Notizen

Wird geladen…