Tetrahydrofuran → HCID 20222944, compound

HRID 979951Notes

Reaction equation

HRID 979951 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].O1CCCC1.[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][N:33]([CH2:36][CH2:37][NH:38][C:39](=O)[CH2:40][C:41]3[C:49]4[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=4)[NH:43][CH:42]=3)[CH2:32][CH2:31]2)=[CH:15][CH:14]=1.[OH-].[Na+]>O>[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][N:33]([CH2:36][CH2:37][NH:38][CH2:39][CH2:40][C:41]3[C:49]4[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=4)[NH:43][CH:42]=3)[CH2:32][CH2:31]2)=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 20222903HCID 20222903, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 20222944HCID 20222944, compoundYield 25.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a stirred mixture of 0.8 parts of lithium aluminum hydride and 135 parts of tetrahydrofuran were added slowly 4 parts of N-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-1H-indol-3-acetamide. The whole was stirred and refluxed overnight. The reaction mixture was cooled in an ice bath and decomposed by the successive additions of 1 part of water, 4.5 parts of a sodium hydroxide solution 15% and 3 parts of water. The whole was filtered over Hyflo and the filtrate was evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (96:4 by volume) saturated with ammonia, as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 1 part (25.5%) of 1-[(4-fluorophenyl)methyl]-N-[1-[2-[[2-(1H-indol-3-yl)ethyl]amino]ethyl]-4-piperidinyl]-1H-benzimidazol-2-amine; mp. 169.7° C. (compound 107).

Workup

  1. temperaturerefluxed overnight
  2. temperatureThe reaction mixture was cooled in an ice bath
  3. filtrationThe whole was filtered over Hyflo
  4. customthe filtrate was evaporated
  5. customThe residue was purified by column chromatography over silica gel using
  6. additiona mixture of trichloromethane and methanol (96:4 by volume) saturated with ammonia
  7. customThe pure fractions were collected
  8. customthe eluent was evaporated
  9. customThe residue was crystallized from acetonitrile

Sources & evidence

ORD record
ord-aff921c50c074c04ba52787e3b472166
Source dataset
uspto-grants-1987_01
Patent number
US04634704

Reaction notes

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