Diethyl Ether → 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxy-3-methyl-cyclopentyl)-N-pyrazin-2-yl-propionamide

HRID 854831Notes

Reaction equation

HRID 854831 reaction equation
C[Mg]Br.CC[O:6][CH2:7][CH3:8].[Cl:9][C:10]1[CH:11]=[C:12]([CH:20]([CH2:30][CH:31]2[CH2:35]C[C:33](=O)[CH2:32]2)[C:21]([NH:23][C:24]2[CH:29]=[N:28][CH:27]=[CH:26][N:25]=2)=[O:22])[CH:13]=[CH:14][C:15]=1[S:16]([CH3:19])(=[O:18])=[O:17]>O1CCCC1>[Cl:9][C:10]1[CH:11]=[C:12]([CH:20]([CH2:30][CH:31]2[CH2:32][CH2:33][C:7]([OH:6])([CH3:8])[CH2:35]2)[C:21]([NH:23][C:24]2[CH:29]=[N:28][CH:27]=[CH:26][N:25]=2)=[O:22])[CH:13]=[CH:14][C:15]=1[S:16]([CH3:19])(=[O:17])=[O:18]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 10477292Piragliatin;RO 4389620HCID 178418573HCID 178418573, compound

Product 1

HCID 100717912-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxy-3-methyl-cyclopentyl)-N-pyrazin-2-yl-propionamideYield 35.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3.0M solution of methylmagnesium bromide in ether (2.53 mL, 7.59 mmol) cooled to 0° C. was treated dropwise with a solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclopentyl)-N-pyrazin-2-yl-propionamide (prepared as in Example 45, 0.10 g, 0.237 mmol) in tetrahydrofuran (1 mL). The resulting solution was stirred at 0° C. for 30 min, quenched with a saturated aqueous ammonium chloride solution (3 mL), and partitioned between a saturated aqueous ammonium chloride solution (20 mL) and ethyl acetate (25 mL). The aqueous layer was extracted with ethyl acetate (25 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 80% ethyl acetate/hexanes) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxy-3-methyl-cyclopentyl)-N-pyrazin-2-yl-propionamide (37 mg, 35%) as a yellow foam: mp 78-84° C. (foam to gel); (ES)+-HRMS m/e calcd for C20H24ClN3O4S (M+H)+ 438.1249. found 438.1254.

Workup

  1. customquenched with a saturated aqueous ammonium chloride solution (3 mL)
  2. custompartitioned between a saturated aqueous ammonium chloride solution (20 mL) and ethyl acetate (25 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (25 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bb0526429be7413b920cfc0e83c4f407
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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