Acetic Acid → N-(3-(1-[3-(1,2-diphenyl-1H-indol-3-yl)propyl]-4-piperidinyl}phenyl)-2-methylpropanamide

HRID 1832242Notes

Reaction equation

HRID 1832242 reaction equation
Cl.[C:2]1([N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)N)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:16][CH:17]([CH3:45])[C:18]([NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]2[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][CH2:35][CH2:36][C:37](=O)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH2:29][CH2:28]2)[CH:22]=1)=[O:19].CC(O)=O.C([O-])([O-])=O.[K+].[K+]>O.[Cl-].[Cl-].[Zn+2]>[C:2]1([N:8]2[C:10]3[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:36]([CH2:35][CH2:34][CH2:33][N:30]3[CH2:31][CH2:32][CH:27]([C:23]4[CH:22]=[C:21]([NH:20][C:18](=[O:19])[CH:17]([CH3:45])[CH3:16])[CH:26]=[CH:25][CH:24]=4)[CH2:28][CH2:29]3)=[C:37]2[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 10738Hydrazine, 1,1-diphenyl-, hydrochloride (1:1)HCID 11430Potassium CarbonateHCID 220493932-methyl-N-(3-[1-(5-oxo-5-phenylpentyl)-4-piperidinyl]phenyl}propanamide

Product 1

HCID 10209625N-(3-(1-[3-(1,2-diphenyl-1H-indol-3-yl)propyl]-4-piperidinyl}phenyl)-2-methylpropanamideYield 37%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1,1-diphenylhydrazine hydrochloride (10.3 mg, 0.0470 mmol), 2-methyl-N-{3-[1-(5-oxo-5-phenylpentyl)-4-piperidinyl]phenyl}propanamide (14.7 mg, 0.0362 mmol), ZnCl2 (14.8 mg, 0.109 mmol), and HOAc (0.500 mL) was heated for 4 h at 80° C. The resulting crude mixture was diluted with water (10 mL), the aqueous layer was neutralized with saturated K2CO3 (10 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic layers were concentrated in vacuo and the residue was purified by preparative TLC plates using 5% of NH3 (2.0 M in methanol) in CH2Cl2 to give the desired product N-(3-{1-[3-(1,2-diphenyl-1H-indol-3-yl)propyl]-4-piperidinyl}phenyl)-2-methylpropanamide (4.10 mg, 37.0%): 1H NMR (400 MHz, CDCl3) δ 7.71–7.65 (m, 1H), 7.42 (d, 1H, J=7.4 Hz), 7.39 (s, 1H), 7.36–7.15 (m, 15H), 6.94 (d, 1H, J=7.8 Hz), 3.12 (d, 2H, J=11.2 Hz), 2.90 (t, 2H, J=7.8 Hz), 2.59–2.45 (m, 3H), 2.19–1.91 (m, 7H), 1.82 (d, 2H, J=13.5 Hz), 1.24 (d, 6H, J=6.9 Hz); ESMS m/e: 555.3 (M+H)+.

Workup

  1. extractionextracted with CH2Cl2 (3×20 mL)
  2. concentrationThe combined organic layers were concentrated in vacuo
  3. customthe residue was purified by preparative TLC plates

Sources & evidence

ORD record
ord-ec4129681d434bc68956502bd9d265f0
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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