Indole-3-Acetic Acid → HCID 20222903, compound

HRID 979939Notes

Reaction equation

HRID 979939 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([OH:13])=O)=[CH:2]1.C(N(CC)CC)C.[I-].ClC1C=CC=C[N+]=1C.[NH2:30][CH2:31][CH2:32][N:33]1[CH2:38][CH2:37][CH:36]([NH:39][C:40]2[N:44]([CH2:45][C:46]3[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=3)[C:43]3[CH:53]=[CH:54][CH:55]=[CH:56][C:42]=3[N:41]=2)[CH2:35][CH2:34]1>ClCCl>[F:52][C:49]1[CH:50]=[CH:51][C:46]([CH2:45][N:44]2[C:43]3[CH:53]=[CH:54][CH:55]=[CH:56][C:42]=3[N:41]=[C:40]2[NH:39][CH:36]2[CH2:37][CH2:38][N:33]([CH2:32][CH2:31][NH:30][C:11](=[O:13])[CH2:10][C:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[NH:1][CH:2]=3)[CH2:34][CH2:35]2)=[CH:47][CH:48]=1

Participants

6

Reactant 4

HCID 802Indole-3-Acetic AcidHCID 8471TriethylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 12891741N-[1-(2-aminoethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine

Product 1

HCID 20222903HCID 20222903, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of 3.5 parts of 1H-indol-3-acetic acid, 4.05 parts of N,N-diethylethanamine and 260 parts of dichloromethane were added 5.1 parts of 2-chloro-1-methylpyridinium iodide and stirring was continued for 15 minutes at room temperature. Then there were added 7.2 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amine and the whole was stirred for 1 hour at room temperature. The reaction mixture was poured onto water and the layers were separated. The organic phase was dried, filtered and 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 4.5 parts (43%) of N-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-1H-indol-3-acetamide; mp. 193.6° C. (compound 77).

Workup

  1. stirringthe whole was stirred for 1 hour at room temperature
  2. additionThe reaction mixture was poured onto water
  3. customthe layers were separated
  4. customThe organic phase was dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (96:4 by volume) saturated with ammonia
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from acetonitrile

Sources & evidence

ORD record
ord-8e7be09b656b4730b7aaaec4aa7eed3f
Source dataset
uspto-grants-1987_01
Patent number
US04634704

Reaction notes

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