Formaldehyde → 5-[[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimdazol-2-yl]amino]-1-piperidinyl]methyl]-2-furanmethanol

HRID 280351

反応式

HRID 280351 の反応式
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][OH:7].[CH2:8]=O.Br.Br.[F:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]2[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[N:22]=[C:21]2[NH:29][CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[CH:15][CH:14]=1>O>[F:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:19][N:20]2[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[N:22]=[C:21]2[NH2:29])=[CH:17][CH:18]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]2[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[N:22]=[C:21]2[NH:29][CH:30]2[CH2:31][CH2:32][N:33]([CH2:8][C:5]3[O:1][C:2]([CH2:6][OH:7])=[CH:3][CH:4]=3)[CH2:34][CH2:35]2)=[CH:15][CH:14]=1

参加物

6

反応物 3

HCID 712FormaldehydeHCID 7361Furfuryl AlcoholHCID 3018631Norastemizole hydrobromide

生成物 2

HCID 30193052-amino-1-((4-fluorophenyl)methyl)-1H-benzimidazoleHCID 136538665-[[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimdazol-2-yl]amino]-1-piperidinyl]methyl]-2-furanmethanol収率 44%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
3 °C

実験手順

A mixture of 30 parts of 2-furanmethanol, 300 parts of a formaldehyde solution 4% in water and 145 parts of 1-[(4-fluorophenyl)-methyl]-N-(4-piperidinyl)-1H-benzimidazol-2-amine dihydrobromide was stirred at 3° C. The mixture was allowed to reach slowly room temperature and stirring was continued for 3 days at room temperature. The reaction mixture was alkalized and extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using first trichloromethane and then a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the (E)-2-butenedioate salt and the free base was liberated again in the conventional manner. It was crystallized from a mixture of 2-propanone and 2,2'-oxybispropane, yielding 57 parts (44%) of 5-[[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimdazol-2-yl]amino]-1-piperidinyl]methyl]-2-furanmethanol; mp. 148.8° C. (compound 47).

後処理

  1. customto reach slowly room temperature
  2. stirringstirring
  3. extractionextracted with dichloromethane
  4. customThe extract was dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography over silica gel using first trichloromethane
  8. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customIt was crystallized from a mixture of 2-propanone and 2,2'-oxybispropane

出典と根拠

ORDレコード
ord-2ba7638ee6c74e9daae5b87a1b075274
出典データセット
uspto-grants-1986_05
特許番号
US04588722

関連ノート

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