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4-Fluorobenzene-1,2-diamine → 5-(5-Fluorobenzimidazol-2-yl)-3-(1-Methylpiperidin-4-yl)-1H-Indole

HRID 278022
Notes
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Reaction equation

HRID 278022 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1)=O.[F:19][C:20]1[CH:25]=[CH:24][C:23]([NH2:26])=[C:22]([NH2:27])[CH:21]=1>[N+](C1C=CC=CC=1)([O-])=O>[F:19][C:20]1[CH:25]=[CH:24][C:23]2[N:26]=[C:1]([C:3]3[CH:4]=[C:5]4[C:9](=[CH:10][CH:11]=3)[NH:8][CH:7]=[C:6]4[CH:12]3[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]3)[NH:27][C:22]=2[CH:21]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 1645844-Fluorobenzene-1,2-diamineHCID 226267865-Formyl-3-(1-Methylpiperidin-4-yl)-1H-Indole

Product 1

HCID 120418115-(5-Fluorobenzimidazol-2-yl)-3-(1-Methylpiperidin-4-yl)-1H-IndoleYield 25%

Reagents, catalysts & solvents 1

HCID 7416NitrobenzeneSolvent

Conditions

Temperature
155 °C

Procedure

A solution of 5-formyl-3-(1-methylpiperidin-4-yl)-1H-indole (0.210 g, 0.90 mmol), and 4-fluoro-o-phenylenediamine (0.112 g, 0.90 mmol), in 15 mL of nitrobenzene was heated, with stirring, at 150-160° C. for 24 hours. An additional 0.5 equivalents of the diamine was added, and heating continued for an additional 24 hours. The solution was allowed to cool to room temperature, the solvent was removed in vacuo, and the residue was purified by silica gel chromatography (dichloromethane:methanol 10:1.5) to give the title compound (0.075 g, 25%) as an amorphous tan solid. FDMS m/e=348 (M+). EA calculated for C21H21N4F.¾ H2O: C, 69.69; H, 6.27; N, 15.48. Found: C, 69.61; H, 6.19; N, 15.17.

Workup

  1. temperatureheating
  2. waitcontinued for an additional 24 hours
  3. temperatureto cool to room temperature
  4. customthe solvent was removed in vacuo
  5. customthe residue was purified by silica gel chromatography (dichloromethane:methanol 10:1.5)

Sources & evidence

ORD record
ord-d4fb135a88004116a74448d718e06f2c
Source dataset
uspto-grants-2002_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06358972B1

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes