Bromine → 3-Bromomethyl-8-fluoro-1-oxo-2-propyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(s)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amide

HRID 884760Notes

Reaction equation

HRID 884760 reaction equation
[Br:1]Br.[CH:3]1([C@H:6]([NH:14][C:15]([C:17]2[C:26]3[C:21](=[C:22]([F:27])[CH:23]=[CH:24][CH:25]=3)[C:20](=[O:28])[N:19]([CH2:29][CH2:30][CH3:31])[C:18]=2[CH3:32])=[O:16])[C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[CH:8]=2)[CH2:5][CH2:4]1>ClCCCl>[CH:3]1([C@H:6]([NH:14][C:15]([C:17]2[C:26]3[C:21](=[C:22]([F:27])[CH:23]=[CH:24][CH:25]=3)[C:20](=[O:28])[N:19]([CH2:29][CH2:30][CH3:31])[C:18]=2[CH2:32][Br:1])=[O:16])[C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[CH:8]=2)[CH2:5][CH2:4]1

Participants

4

Reactant 2

HCID 24408BromineHCID 592530488-Fluoro-3-methyl-1-oxo-2-propyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amide

Product 1

HCID 592530143-Bromomethyl-8-fluoro-1-oxo-2-propyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(s)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amide

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

Bromine (400 mg, 2.5 mmol) in 0.5 ml 1,2-dichloroethane was added to 8-fluoro-3-methyl-1-oxo-2-propyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amide (344 mg, 0.84 mmol, see example 3) in 1,2-dichloroethane (20 mL) at 60° C. The reaction mixture was stirred for 15 minutes at 60° C. The reaction mixture was concentrated in vacuo to give crude 3-bromomethyl-8-fluoro-1-oxo-2-propyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amide, which was used in the next step without purification. LC-MS (m/z) 489.5 (MH+); tR=1.55.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-d40b9a40df174c09bab53560765c64c9
Source dataset
uspto-grants-2012_08
Patent number
US08242134B2

Reaction notes

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