Oxalyl chloride → 3-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-(2-oxo-2,3-dihydro-pyrimidin-4-yl)-propionamide

HRID 398707Notes

Reaction equation

HRID 398707 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[C:13]([C:21]([F:24])([F:23])[F:22])[CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH:31]1[CH:38]=[CH:37][C:35]([NH2:36])=[N:34][C:32]1=[O:33].C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O.O1CCCC1>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[C:13]([C:21]([F:24])([F:22])[F:23])[CH:12]=2)[C:8]([NH:36][C:35]2[NH:34][C:32](=[O:33])[N:31]=[CH:38][CH:37]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 120695043-Cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionic acidHCID 178418229Cytosine

Product 1

HCID 223153053-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-(2-oxo-2,3-dihydro-pyrimidin-4-yl)-propionamideYield 53.7%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionic acid (183 mg, 0.50 mmol) in methylene chloride (5 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.30 mL, 0.56 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 15 min and at 25° C. for 30 min. The reaction mixture was then treated with a solution of cytosine (116.7 mg, 1.06 mmol) in tetrahydrofuran (2.0 mL) and N,N-dimethylformamide (2.0 mL) followed by N,N-diisopropylethylamine (0.20 mL, 1.20 mmol). This solution was stirred at 25° C. for 18 h. At this time, the reaction was concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 90/10 methylene chloride/methanol) afforded 3-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-(2-oxo-2,3-dihydro-pyrimidin-4-yl)-propionamide (100 mg, 53.7%) as a white solid: mp 236-238° C.; EI-HRMS m/e calcd for C20H22F3N3O4S (M+) 457.1283, found 457.1291.

Workup

  1. stirringThis solution was stirred at 25° C. for 18 h
  2. concentrationAt this time, the reaction was concentrated in vacuo

Sources & evidence

ORD record
ord-f720968d03a649bfbeeb6d5f53792268
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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