HCID 178506482, compound → HCID 10480705, compound

HRID 719918Notes

Reaction equation

HRID 719918 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:30][CH:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)[C:13]([NH:15][C:16]2[N:17]=[CH:18][C:19]([C:22]([O:24][NH:25]/[C:26](=[N:28]\[H])/[CH3:27])=O)=[N:20][CH:21]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:30][CH:31]2[CH2:32][CH2:33][CH2:34][CH2:35]2)[C:13]([NH:15][C:16]2[CH:21]=[N:20][C:19]([C:22]3[O:24][N:25]=[C:26]([CH3:27])[N:28]=3)=[CH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

3

Reactant 1

HCID 178506482HCID 178506482, compound

Product 1

HCID 10480705HCID 10480705, compoundYield 13.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of crude (Z)-N-[[[5-[[2(R)-(3-chloro-4-methylsulfonyl-phenyl)-3-cyclopentyl-1-oxopropyl]amino]-2-pyrazinyl]carbonyl]oxy]ethanimidamide (0.331 mmol) in toluene (3.6 mL) was treated with 4 Å molecular sieves and warmed to 80° C. where it stirred for 48 h. The reaction was then partitioned between ethyl acetate (25 mL) and water (50 mL). The organic layer was washed with a 1N aqueous hydrochloric acid solution (50 mL). The combined aqueous layers were then back-extracted with ethyl acetate (50 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 2/3 ethyl acetate/hexanes) afforded impure 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-methyl-[1,2,4]oxadiazol-5-yl)-pyrazin-2-yl]-propionamide as a light yellow foam (22.5 mg, 13%). The impure product was re-purified by reverse phase high-performance liquid chromatography (Waters symmetry packing, acetonitrile/water with 0.05% trifluoroacetic acid, 2% to 45% acetonitrile gradient). The fractions containing product were concentrated in vacuo and lyophilized to afford 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-methyl-[1,2,4]oxadiazol-5-yl)-pyrazin-2-yl]-propionamide (12 mg, 7%) as a white lyophilized solid: mp 101–105° C. (foam to gel); (ES)+-HRMS m/e calcd for C22H24ClN5O4S (M+H)+ 490.1311, found 490.1315.

Workup

  1. customThe reaction was then partitioned between ethyl acetate (25 mL) and water (50 mL)
  2. washThe organic layer was washed with a 1N aqueous hydrochloric acid solution (50 mL)
  3. extractionThe combined aqueous layers were then back-extracted with ethyl acetate (50 mL)
  4. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution (50 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9b0e53d427f5415ab80c64eb1b23ca4e
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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