Sodium borohydride → 7-(3-hydroxymethyl-2-oxopyrrolidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

HRID 1162910Notes

Reaction equation

HRID 1162910 reaction equation
[O:1]=[C:2]1[CH:6]([C:7](OCC)=[O:8])[CH2:5][CH2:4][N:3]1[C:12]1[CH:21]=[C:20]2[C:15]([CH:16]=[C:17]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]([F:32])([F:31])[F:30])[NH:18][C:19]2=[O:22])=[CH:14][CH:13]=1.[BH4-].[Na+].[Cl-].[Ca+2].[Cl-]>CO>[OH:8][CH2:7][CH:6]1[CH2:5][CH2:4][N:3]([C:12]2[CH:21]=[C:20]3[C:15]([CH:16]=[C:17]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[C:29]([F:32])([F:30])[F:31])[NH:18][C:19]3=[O:22])=[CH:14][CH:13]=2)[C:2]1=[O:1]

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 11854958Ethyl 2-oxo-1-[1-oxo-3-(2-trifluoromethylphenyl)-1,2-dihydroisoquinolin-7-yl]pyrrolidine-3-carboxylate

Product 1

HCID 118549597-(3-hydroxymethyl-2-oxopyrrolidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-oneYield 50%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The 2-oxo-1-[1-oxo-3-(2-trifluoromethylphenyl)-1,2-dihydroisoquinolin-7-yl]pyrrolidin-3-carboxylic acid ethyl (11 mg, 0.025 mmol) prepared in step B of Example 1-45, sodium borohydride (9.5 mg, 0.25 mmol), and calcium chloride (27.7 mg, 0.25 mmol) were dissolved in methanol (5 ml), and the obtained solution was then stirred at a room temperature for 16 hours. Thereafter, the reaction solution was concentrated, and it was then purified using ODS cartridge 5 g (Mega Bond Elut (registered trademark) C18, manufactured by Varian; water methanol=1:0 to 0:1). The resultant was then preparatively separated by preparative HPLC (column: Combi ODS (φ: 28.0 mm×50 mm) manufactured by Wako; developing solvent: 0.05% trifluoroacetic acid-containing water: 0.05% trifluoroacetic acid-containing acetonitrile=90:10 to 5:95), so as to obtain 7-(3-hydroxymethyl-2-oxopyrrolidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (5 mg, 50%) in the form of a white amorphous substance.

Workup

  1. concentrationThereafter, the reaction solution was concentrated
  2. customit was then purified
  3. customThe resultant was then preparatively separated by preparative HPLC (column: Combi ODS (φ: 28.0 mm×50 mm) manufactured by Wako; developing solvent: 0.05% trifluoroacetic acid-containing water: 0.05% trifluoroacetic acid-containing acetonitrile=90:10 to 5:95)

Sources & evidence

ORD record
ord-127176f2c44d4327990ceafe949eb026
Source dataset
uspto-grants-2010_10
Patent number
US07820693B2

Reaction notes

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