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

HRID 222678Notes

Reaction equation

HRID 222678 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-5e1d2d1d4b4d4f5d8a01fc84b3277e90
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

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