trans-2-Phenyl-1-cyclopropanecarbonyl chloride → trans-2-Phenyl-cyclopropanecarboxylic acid (1-acetyl-2,3-dihydro-1H-indol-6-yl)-(1-benzyl-piperidin-4-yl)-amide

HRID 2250869Notes

Reaction equation

HRID 2250869 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:23]=[C:22]3[C:18]([CH2:19][CH2:20][N:21]3[C:24](=[O:26])[CH3:25])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:36]1([C@@H:42]2[CH2:44][C@H:43]2[C:45](Cl)=[O:46])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>C(#N)C>[C:24]([N:21]1[C:22]2[C:18](=[CH:17][CH:16]=[C:15]([N:14]([CH:11]3[CH2:12][CH2:13][N:8]([CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH2:9][CH2:10]3)[C:45]([C@@H:43]3[CH2:44][C@H:42]3[C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[O:46])[CH:23]=2)[CH2:19][CH2:20]1)(=[O:26])[CH3:25]

Participants

5

Reactant 3

HCID 13656trans-2-Phenyl-1-cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 27611281-Acetyl-N-(1-benzylpiperidin-4-yl)-indolin-6-amine

Product 1

HCID 69212174trans-2-Phenyl-cyclopropanecarboxylic acid (1-acetyl-2,3-dihydro-1H-indol-6-yl)-(1-benzyl-piperidin-4-yl)-amideYield 61%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 1-[6-(1-benzyl-piperidin-4-ylamino)-2,3-dihydro-indol-1-yl]-ethanone (0.353 g, 1.01 mmol) in 50 mL of acetonitrile was added diisopropylethylamine (0.193 mL, 1.11 mmol) and trans-2-phenyl-1-cyclopropanecarbonyl chloride (90%, 0.174 mL, 1.01 mmol). The reaction mixture was stirred overnight, and then was filtered through diatomaceous earth. The filtrate was evaporated and the residue was chromatographed over silica gel (acetone/MeOH/CH2Cl2) to provide the desired product as a tan solid (0.30 g, 61%). 1H NMR (400 MHz, CDCl3): 8.04 (s, 1H), 7.38-6.98 (m, 9H), 6.97-6.82 (m, 2H), 6.76 (dd, J=12.5, 6.2 Hz, 1H), 4.65 (br t, J=12.7 Hz, 1H), 4.12 (t, J=9.5 Hz, 1H), 4.09-3.87 (m, 1H), 3.44 (s, 2H), 3.26-3.07 (m, 2H), 2.97-2.79 (m, 2H), 2.51-2.47 (m, 1H), 2.29-1.98 (m, 5H), 1.92-1.66 (m, 2H), 1.65-1.29 (m, 4H), 1.08-0.96 (m, 1H). MS: exact mass calculated for C32H35N3O2, 493.27; m/z found, 494.3 [M+H]+.

Workup

  1. filtrationwas filtered through diatomaceous earth
  2. customThe filtrate was evaporated
  3. customthe residue was chromatographed over silica gel (acetone/MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-8d2b085bc346421e8a5fb2fe046a1048
Source dataset
uspto-grants-2008_01
Patent number
US07317025B2

Reaction notes

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