p-Toluenesulfonic acid monohydrate → N-(5-acetyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

HRID 719929Notes

Reaction equation

HRID 719929 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:28][CH:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)[C:13]([NH:15][C:16]2[CH:21]=[N:20][C:19]([C:22](OC)([O:24]C)[CH3:23])=[CH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)=O.O.C(OCC)(=O)C>[C:22]([C:19]1[N:20]=[CH:21][C:16]([NH:15][C:13](=[O:14])[C@@H:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([Cl:1])[CH:3]=2)[CH2:28][CH:29]2[CH2:30][CH2:31][CH2:32][CH2:33]2)=[N:17][CH:18]=1)(=[O:24])[CH3:23]

Participants

6

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 674826772(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1,1-dimethoxy-ethyl)-pyrazin-2-yl]-propionamide

Product 1

HCID 10253195N-(5-acetyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamideYield 96.7%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1,1-dimethoxy-ethyl)-pyrazin-2-yl]-propionamide (1.22 g, 2.459 mmol) in acetone (28 mL) and water (3 mL) was treated with p-toluenesulfonic acid monohydrate (142.5 mg, 0.738 mmol). The reaction mixture was heated to 60° C. for 30 min and then was diluted with ethyl acetate (100 mL). The organic layer was washed with a saturated aqueous sodium bicarbonate solution (100 mL), water (100 mL), and a saturated aqueous sodium chloride solution (100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 1/3 ethyl acetate/hexanes) afforded the N-(5-acetyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide as a white foam (1.07 g, 96%): mp 77–80° C. (foam to gel); (ES)+-HRMS m/e calcd for C21H24ClN3O4S (M+H)+ 450.1249, found 450.1253.

Workup

  1. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (100 mL), water (100 mL)
  2. dry with materiala saturated aqueous sodium chloride solution (100 mL), dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b53e0cc684d94e299b5ab36a074a54d6
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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