1-Bromo-2-Chloroethane → 3-(2-(4-(2-Chloroethoxy)benzyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-N-cyclopropyl-4-methylbenzamide

HRID 907267Notes

Reaction equation

[CH:1]1([NH:4][C:5](=[O:32])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[C:19](=[O:23])[N:18]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=3)[CH:17]=[CH:16]4)[CH:7]=2)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:40][CH2:41][Cl:42]>CN(C=O)C.C(OCC)(=O)C>[Cl:42][CH2:41][CH2:40][O:31][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][N:18]2[CH:17]=[CH:16][C:15]3[C:20](=[CH:21][CH:22]=[C:13]([C:8]4[CH:7]=[C:6]([CH:11]=[CH:10][C:9]=4[CH3:12])[C:5]([NH:4][CH:1]4[CH2:2][CH2:3]4)=[O:32])[CH:14]=3)[C:19]2=[O:23])=[CH:30][CH:29]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of the product of step i) (500 mg) in DMF (10 mL) was added potassium carbonate (820 mg) and 1-bromo-2-chloroethane (0.2 mL) and the reaction was heated at 50° C. for 22 hours. Additional 1-bromo-2-chloroethane (0.3 mL) and potassium carbonate (820 mg) were added and heating continued for 40 hours. The reaction mixture was diluted with ethyl acetate and filtered. The filtrate was washed with water and brine, dried over magnesium sulphate and evaporated. The residue was purified (SiO2, ethyl acetate:isohexane (6:4)) to yield the sub-titled compound (280 mg).

Workup

temperatureheating
filtrationfiltered
washThe filtrate was washed with water and brine
dry with materialdried over magnesium sulphate
customevaporated
customThe residue was purified (SiO2, ethyl acetate:isohexane (6:4))

Sources & evidence

ORD record: ord-b847f48e3d454210b145d696222aa77c
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012979B2

Reaction notes

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