Dichloromethane → 2-(3-Fluoro-4-trifluoromethyl-phenyl)-N-{2-[(R)-2-(3-hydroxy-azetidin-1-yl)-1-methyl-ethyl]-6-methyl-1-oxo-1,2-dihydro-isoquinolin-5-yl}-acetamide

HRID 418545Notes

Reaction equation

CS(O[CH2:6][C@H:7]([N:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH3:34])[C:15]=2[NH:19][C:20](=[O:33])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[C:24]([F:32])[CH:23]=2)[C:10]1=[O:35])[CH3:8])(=O)=O.Cl.[OH:37][CH:38]1[CH2:41][NH:40][CH2:39]1.C(N(CC)CC)C.C(Cl)Cl>>[F:32][C:24]1[CH:23]=[C:22]([CH2:21][C:20]([NH:19][C:15]2[C:14]([CH3:34])=[CH:13][CH:12]=[C:11]3[C:16]=2[CH:17]=[CH:18][N:9]([C@H:7]([CH3:8])[CH2:6][N:40]2[CH2:41][CH:38]([OH:37])[CH2:39]2)[C:10]3=[O:35])=[O:33])[CH:27]=[CH:26][C:25]=1[C:28]([F:31])([F:29])[F:30]

Participants

Reactant 4

HCID 6344Dichloromethane

HCID 8471Triethylamine

HCID 27592903-Hydroxyazetidine hydrochloride

HCID 59845709(R)-2-(5-(2-(3-Fluoro-4-(trifluoromethyl)phenyl)acetamido)-6-methyl-1-oxoisoquinolin-2(1H)-yl)propyl methanesulfonate

Product 1

HCID 250141082-(3-Fluoro-4-trifluoromethyl-phenyl)-N-{2-[(R)-2-(3-hydroxy-azetidin-1-yl)-1-methyl-ethyl]-6-methyl-1-oxo-1,2-dihydro-isoquinolin-5-yl}-acetamide

Procedure

A solution of (R)-2-(5-(2-(3-fluoro-4-(trifluoromethyl)phenyl)acetamido)-6-methyl-1-oxoisoquinolin-2(1H)-yl)propyl methanesulfonate (100 mg, 0.2 mmol), 3-hydroxyazetidine hydrochloride (120 mg, 1.1 mmol), triethylamine (200 mg, 2 mmol) and methylene chloride (1 mL, 20 mmol) was stirred at room temperature overnight. The volatiles were removed and the residue was purified by reverse phase preparative HPLC to afford the desired product as a white solid.

Workup

customThe volatiles were removed
customthe residue was purified by reverse phase preparative HPLC

Sources & evidence

ORD record: ord-e2eabfc9e354440dabab0d6d4beee60c
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093265B2

Reaction notes

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