Methanesulfinic acid → 2(r)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-n-(5-methanesulfonylmethyl-pyrazin-2-yl)-propionamide

HRID 719906Notes

Reaction equation

HRID 719906 reaction equation
Br[CH2:2][C:3]1[N:4]=[CH:5][C:6]([NH:9][C:10](=[O:29])[C@@H:11]([C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[C:20]([Cl:28])[CH:19]=2)[CH2:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[N:7][CH:8]=1.[Na].[CH3:31][S:32]([OH:34])=[O:33]>CC(C)=O>[Cl:28][C:20]1[CH:19]=[C:18]([C@@H:11]([CH2:12][CH:13]2[CH2:14][CH2:15][CH2:16][CH2:17]2)[C:10]([NH:9][C:6]2[CH:5]=[N:4][C:3]([CH2:2][S:32]([CH3:31])(=[O:34])=[O:33])=[CH:8][N:7]=2)=[O:29])[CH:23]=[CH:22][C:21]=1[S:24]([CH3:27])(=[O:25])=[O:26]

Participants

5

Reactant 3

HCID 87251Methanesulfinic acid2×HCID 5360545Sodium2×HCID 67482634N-(5-bromomethyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Product 1

HCID 100516792(r)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-n-(5-methanesulfonylmethyl-pyrazin-2-yl)-propionamideYield 74.9%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-(5-bromomethyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (prepared as in Example 30, 102.2 mg, 0.20 mmol) in acetone (1 mL) was cooled to 0° C. and then treated with the sodium salt of methanesulfinic acid (31.8 mg, 0.30 mmol). The reaction stirred at 0° C. for 1 h and then at 25° C. for 4 h 20 min. A second aliquot of the sodium salt of methanesulfinic acid (24.0 mg, 0.24 mmol) was added, and the reaction was stirred at 25° C. overnight. The reaction was then concentrated in vacuo. The residue was diluted with ethyl acetate (50 mL), washed with water (2×25 mL) and a saturated aqueous sodium chloride solution (25 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-methanesulfonylmethyl-pyrazin-2-yl)-propionamide (74.9 mg, 73%) as a white foam: mp 91–95° C. (foam to gel); (ES)+-HRMS m/e calcd for C21H26ClN3O5S2 (M+H)+ 500.1075, found 500.1080.

Workup

  1. waitat 25° C. for 4 h 20 min
  2. stirringthe reaction was stirred at 25° C. overnight
  3. concentrationThe reaction was then concentrated in vacuo
  4. additionThe residue was diluted with ethyl acetate (50 mL)
  5. washwashed with water (2×25 mL)
  6. dry with materiala saturated aqueous sodium chloride solution (25 mL), dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ce3d156b43da4244ba9fde5f21353dc0
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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