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

HRID 13130

반응식

HRID 13130 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

(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.

후처리

  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)

출처 및 근거

ORD 기록
ord-ad49fd55b692495fa7edb0d6eaadbea5
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07728030B2

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