1,2-Dichloroethane → N-[2-(2-methylpiperidin-1-yl)ethyl]-4-(2-phenyl-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamide

HRID 2064564Notes

Reaction equation

HRID 2064564 reaction equation
[C:1]1([C:7]2[N:8]([C:16]3[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=3)[C:9]3[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=3[CH:15]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][N:27]1[CH2:32][CH2:33][NH2:34].C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][N:27]1[CH2:32][CH2:33][NH:34][C:20](=[O:21])[C:19]1[CH:18]=[CH:17][C:16]([N:8]2[C:9]3[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=3[CH:15]=[C:7]2[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 31492632-(2-Methylpiperidin-1-yl)ethan-1-amineHCID 66233704-(2-phenyl-4,5,6,7-tetrahydro-1H-indol-1-yl)benzoic acid2×

Product 1

HCID 22521993N-[2-(2-methylpiperidin-1-yl)ethyl]-4-(2-phenyl-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamideYield 80%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of DCM containing 4-(2-phenyl-4,5,6,7-tetrahydro-1H-indol-1-yl)benzoic acid (Intermediate 7, 1 eq.) was stirred at room temperature, DMAP (1.1 equivalent) and 2-(2-methylpiperidin-1-yl)ethanamine (1 eq.) were added. The reaction mixture was then cooled down to 0° C. and EDC (1.1 eq.) was added portion-wise. After stirring for 1 hour at 0° C., the reaction mixture was allowed to warm to room temperature. The reaction was monitored by TLC and LC/MS. Usually after 12 hours stirring at RT, the reaction mixture was hydrolyzed, washed with sodium carbonate solution (10%), dried over MgSO4, and evaporated in vacuo to give a crude product. Flash chromatography on silica gel, eluting with 60% EtOAc in hexane gave, after evaporation, the expected product N-[2-(2-methylpiperidin-1-yl)ethyl]-4-(2-phenyl-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamide (1) as a beige solid, in 80% yield (96% purity by HPLC). MS(ESI+): 442.7; MS(ESI−): 440.5.

Workup

  1. temperatureThe reaction mixture was then cooled down to 0° C.
  2. stirringAfter stirring for 1 hour at 0° C.
  3. temperatureto warm to room temperature
  4. stirringUsually after 12 hours stirring at RT
  5. washwashed with sodium carbonate solution (10%)
  6. dry with materialdried over MgSO4
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-f61b636958ba4875bfba414bf8de55b8
Source dataset
uspto-grants-2012_10
Patent number
US08288432B2

Reaction notes

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