Dichloromethane → 3-tert-butoxycarbonyl-7-chloro-6-[3-(2-oxo-2,3-dihydro-indol-1-yl)-propylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041602Notes

Reaction equation

HRID 2041602 reaction equation
[OH-].[K+].[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[C:17]([S:22]C(=O)N(C)C)=[C:18]([Cl:21])[CH:19]=[CH:20][C:13]=2[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl[CH2:29][CH2:30][CH2:31][N:32]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][C:33]1=[O:41].ClCCl>CO.O>[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[C:17]([S:22][CH2:29][CH2:30][CH2:31][N:32]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[CH2:34][C:33]3=[O:41])=[C:18]([Cl:21])[CH:19]=[CH:20][C:13]=2[CH2:12][CH2:11]1)=[O:9])([CH3:5])([CH3:6])[CH3:4]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 14797Potassium HydroxideHCID 180699061-(3-Chloropropyl)indolin-2-oneHCID 576559793-tert-butoxycarbonyl-7-chloro-6-dimethylaminocarbonylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 667071123-tert-butoxycarbonyl-7-chloro-6-[3-(2-oxo-2,3-dihydro-indol-1-yl)-propylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Add potassium hydroxide (899 mg, 16.64 mmol) in one portion to a solution of 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (200 mg, 0.52 mmol) in methanol (10 mL). Heat the reaction to 50° C. under nitrogen for 24 h, then cool to room temperature and add 1-(3-chloro-propyl)-1,3-dihydro-indol-2-one (217 mg, 1.04 mmol). Stir the reaction at room temperature for 4 days. Remove solvents in vacuo, add dichloromethane (20 mL) and water (20 mL). Remove the organic layer and dry using an ISCO® phase separator then concentrate in vacuo to give 3-tert-butoxycarbonyl-7-chloro-6-[3-(2-oxo-2,3-dihydro-indol-1-yl)-propylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as orange powder. MS (ES+) m/z: 509 (M+Na)+.

Workup

  1. temperatureHeat
  2. customthe reaction to 50° C. under nitrogen for 24 h
  3. customthe reaction at room temperature for 4 days
  4. customRemove the organic layer
  5. customdry
  6. concentrationthen concentrate in vacuo

Sources & evidence

ORD record
ord-764586f44de9414d94dc91d4a1da86b8
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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