Isopropyl isocyanate → 4-(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy)-piperidine-1-carboxylic acid isopropyl amide

HRID 645812Notes

Reaction equation

HRID 645812 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[C:13]([O:16][CH:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[CH:14]=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[CH:23]([N:26]=[C:27]=[O:28])([CH3:25])[CH3:24]>ClCCl>[CH:23]([NH:26][C:27]([N:20]1[CH2:21][CH2:22][CH:17]([O:16][C:13]2[CH:14]=[CH:15][C:8]3[CH2:7][CH2:6][N:5]([CH:1]4[CH2:2][CH2:3][CH2:4]4)[CH2:11][CH2:10][C:9]=3[CH:12]=2)[CH2:18][CH2:19]1)=[O:28])([CH3:25])[CH3:24]

Participants

4

Reactant 2

HCID 61277Isopropyl isocyanateHCID 685061053-cyclobutyl-7-(piperidin-4-yloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 103854244-(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy)-piperidine-1-carboxylic acid isopropyl amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-cyclobutyl-7-(piperidin-4-yloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (E6) (150 mg, 0.5 mmol) and isopropyl isocyanate (60 μL, 0.6 mmol) in dichloromethane (5 ml) was stirred at room temperature for 16 hours. The solution was concentrated in vacuo and the residue was purified by column chromatography eluting with dichloromethane then a mixture of 0.880 ammonia:ethanol:dichloromethane (1:9:90) to afford the title product (E66). MS (ES+) m/e 386 [M+H]+.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. customthe residue was purified by column chromatography
  3. washeluting with dichloromethane
  4. additiona mixture of 0.880 ammonia:ethanol:dichloromethane (1:9:90)

Sources & evidence

ORD record
ord-3dd9a597d30b45e0bdaa949dcdfb8453
Source dataset
uspto-grants-2010_04
Patent number
US07704994B2

Reaction notes

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