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

HRID 13130

反応式

HRID 13130 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

(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.

後処理

  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)

出典と根拠

ORDレコード
ord-ad49fd55b692495fa7edb0d6eaadbea5
出典データセット
uspto-grants-2010_06
特許番号
US07728030B2

関連ノート

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