Acetic Acid → 2-methyl-N-(3-{1-[3-(1-methyl-1H-indol-3-yl)propyl]-4-piperidinyl}phenyl)propanamide

HRID 1832609Notes

Reaction equation

HRID 1832609 reaction equation
O1CCO[CH:2]1[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][CH:13]([C:16]2[CH:17]=[C:18]([NH:22][C:23](=[O:27])[CH:24]([CH3:26])[CH3:25])[CH:19]=[CH:20][CH:21]=2)[CH2:12][CH2:11]1.[CH3:28][N:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)N.CC(O)=O.C([O-])([O-])=O.[K+].[K+]>O.[Cl-].[Cl-].[Zn+2]>[CH3:25][CH:24]([CH3:26])[C:23]([NH:22][C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([CH:13]2[CH2:14][CH2:15][N:10]([CH2:9][CH2:8][CH2:7][C:6]3[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:29]([CH3:28])[CH:2]=3)[CH2:11][CH2:12]2)[CH:17]=1)=[O:27]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 36299N-methyl-N-phenyl-hydrazineHCID 22048802N-(3-{1-[4-(1,3-dioxolan-2-yl)butyl]4-piperidinyl}phenyl)-2-methylpropanamide

Product 1

HCID 220491202-methyl-N-(3-{1-[3-(1-methyl-1H-indol-3-yl)propyl]-4-piperidinyl}phenyl)propanamideYield 18.7%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

Prepared by Procedure H and Scheme S. A mixture of N-(3-{1-[4-(1,3-dioxolan-2-yl)butyl]-4-piperidinyl}phenyl)-2-methylpropanamide (100 mg, 0.270 mmol), 1-methyl-1-phenylhydrazine (106 mg, 0.870 mmol), ZnCl2 (119 mg, 0.870 mmol) and HOAc (1.00 mL) was heated for 12 h at 80° C. The resulting crude mixture was diluted with water (20 mL), the aqueous layer was neutralized with a saturated K2CO3 solution (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 using 3% of NH3 (2.0 M in methanol) in CH2Cl2 to give the desired product 2-methyl-N-(3-{1-[3-(1-methyl-1H-indol-3-yl)propyl]-4-piperidinyl}phenyl)propanamide (20.7 mg, 18.7%): 1H NMR (400 MHz, CDCl3) δ 7.60 (d, 1H, J=8.1 Hz), 7.45 (s, 1H), 7.35 (d, 1H, J=7.4 Hz), 7.25 (m, 4H), 7.09 (t, 1H, J=7.3 Hz), 6.97 (d, 1H, J=7.3 Hz), 6.86 (s, 1H), 3.75 (s, 3H) 3.11 (d, 2H, J=11.6 Hz), 2.79 (t, 2H, J=7.3 Hz), 2.51 (m, 4H), 2.12–1.81 (m, 8H), 1.25 (d, 6H, J=7.1 Hz); Anal. Calcd for C27H35N3O+0.225CHCl3: C, 73.57; H, 7.99; N, 9.45. Found: C, 73.93; H, 7.90; N, 9.23; ESMS m/e: 418.2 (M+H)+.

Workup

  1. customPrepared by Procedure H and Scheme S
  2. extractionextracted with CH2Cl2 (3×20 mL)
  3. concentrationThe combined organic layers were concentrated in vacuo
  4. customthe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-df6d2fcd082040e888e2d0ce778921ee
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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