Triethylamine → Methanesulfonic acid 2-oxo-1-[1-oxo-3-(2-trifluoromethylphenyl)-1,2-dihydroisoquinolin-7-yl]-pyrrolidin-3-ylmethyl ester

HRID 1162924Notes

Reaction equation

HRID 1162924 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].C(N(CC)CC)C.[OH:13][CH2:14][CH:15]1[CH2:19][CH2:18][N:17]([C:20]2[CH:29]=[C:28]3[C:23]([CH:24]=[C:25]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[C:37]([F:40])([F:39])[F:38])[NH:26][C:27]3=[O:30])=[CH:22][CH:21]=2)[C:16]1=[O:41].[Cl-].[NH4+]>ClCCl>[O:41]=[C:16]1[CH:15]([CH2:14][O:13][S:2]([CH3:1])(=[O:4])=[O:3])[CH2:19][CH2:18][N:17]1[C:20]1[CH:29]=[C:28]2[C:23]([CH:24]=[C:25]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:37]([F:40])([F:38])[F:39])[NH:26][C:27]2=[O:30])=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 118549597-(3-hydroxymethyl-2-oxopyrrolidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

Product 1

HCID 86626744Methanesulfonic acid 2-oxo-1-[1-oxo-3-(2-trifluoromethylphenyl)-1,2-dihydroisoquinolin-7-yl]-pyrrolidin-3-ylmethyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

Methanesulfonyl chloride (0.023 ml, 0.299 mmol) and triethylamine (0.03 ml, 0.299 mmol) were added at −20° C. to a dichloromethane solution (2 ml) that contained the 7-(3-hydroxymethyl-2-oxopyrrolidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (80 mg, 199 mmol) obtained in Example 1-46. The obtained mixture was stirred at −20° C. for 2 hours. Thereafter, a saturated ammonium chloride aqueous solution was added to the reaction solution, and the obtained mixture was then extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was then distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=30:1->20:1), so as to obtain methanesulfonic acid 2-oxo-1-[1-oxo-3-(2-trifluoromethylphenyl)-1,2-dihydroisoquinolin-7-yl]-pyrrolidin-3-ylmethyl ester (38 mg, 40%) in the form of a colorless oil substance.

Workup

  1. extractionthe obtained mixture was then extracted with ethyl acetate
  2. dry with materialThe extract was dried over anhydrous sodium sulfate
  3. distillationthe solvent was then distilled away under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=30:1->20:1)

Sources & evidence

ORD record
ord-e5ad0d6e08e54926a9b6d87a0285a3bb
Source dataset
uspto-grants-2010_10
Patent number
US07820693B2

Reaction notes

Loading…