Water → methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-1H-benzimidazole-6-carboxylate

HRID 1691744ノート

反応式

HRID 1691744 の反応式
Cl[C:2]1[NH:6][C:5]2[CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[CH:9]=[CH:10][C:4]=2[N:3]=1.[F:15][C:16]1[CH:17]=[C:18]([CH:22]2[CH:27]([CH2:28][N:29]([C@@H:37]([C:39]3[C:48]4[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=4)[CH:42]=[CH:41][CH:40]=3)[CH3:38])[C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:26][CH2:25][NH:24][CH2:23]2)[CH:19]=[CH:20][CH:21]=1.O>CS(C)=O>[C:32]([O:31][C:30]([N:29]([CH2:28][CH:27]1[CH2:26][CH2:25][N:24]([C:2]2[NH:6][C:5]3[CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[CH:9]=[CH:10][C:4]=3[N:3]=2)[CH2:23][CH:22]1[C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([F:15])[CH:17]=1)[C@@H:37]([C:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH:42]=[CH:41][CH:40]=1)[CH3:38])=[O:36])([CH3:33])([CH3:34])[CH3:35]

参加物

5

反応物 3

HCID 962WaterHCID 11543028Methyl 2-chloro-1H-benzo[d]imidazole-5-carboxylateHCID 59178728tert-butyl {[3-(3-fluorophenyl)piperidin-4-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate

生成物 1

HCID 66905807methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-1H-benzimidazole-6-carboxylate収率 34.9%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

A solution of 313 mg of methyl 2-chloro-1H-benzimidazole-6-carboxylate and 100 mg of tert-butyl {[3-(3-fluorophenyl)piperidin-4-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate in 2.00 mL of DMSO was stirred at 130° C. for 9 hours. The reaction mixture was cooled to room temperature, and water was then added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 48 mg of methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-1H-benzimidazole-6-carboxylate as a pale yellow solid. ESI+: 637

後処理

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

出典と根拠

ORDレコード
ord-7135e57c40114ab8b7252179bb0af293
出典データセット
uspto-grants-2012_04
特許番号
US08153658B2

反応ノート

読み込み中…