Hydrochloric Acid → 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-pyrazin-2-yl-propionamide

HRID 1355282Notes

Reaction equation

HRID 1355282 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:13]([CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:14](O)=[O:15])[CH:6]=[CH:7][C:8]=1[S:9]([CH3:12])(=[O:11])=[O:10])#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:29][C:30]1[CH:35]=[N:34][CH:33]=[CH:32][N:31]=1.C(N(CC)CC)C.Cl>C(Cl)Cl.CN(C)C=O.O.C(OCC)(=O)C>[C:1]([C:3]1[CH:4]=[C:5]([CH:13]([CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:14]([NH:29][C:30]2[CH:35]=[N:34][CH:33]=[CH:32][N:31]=2)=[O:15])[CH:6]=[CH:7][C:8]=1[S:9]([CH3:12])(=[O:10])=[O:11])#[N:2]

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 78747AminopyrazineHCID 120694992-(3-Cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid

Product 1

HCID 223151802-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-pyrazin-2-yl-propionamide

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 75, 200 mg, 0.622 mmol) in methylene chloride (5 mL) was treated with N,N-dimethylformamide (2 drops) and then cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (0.081 mL, 0.933 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred for 1 h. The reaction mixture was then concentrated in vacuo. The resulting yellow gel was diluted with methylene chloride (2 mL) and then slowly added to a mixture of 2-aminopyrazine (89 mg, 0.933 mmol) and triethylamine (0.173 mL, 1.24 mmol) in N,N-dimethylformamide (3 mL). The resulting reaction mixture was stirred at 25° C. for 24 h. The reaction mixture was then diluted with water (30 mL), a 1N aqueous hydrochloric acid solution (5 mL), and ethyl acetate (30 mL). The layers were separated, and the organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 19/1 methylene chloride/methanol) afforded 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-pyrazin-2-yl-propionamide as an impure orange foam. Re-purification by flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/1 hexanes/ethyl acetate) afforded 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-pyrazin-2-yl-propionamide (8 mg, 3%) as a yellow foam: mp 88–93° C. (foam to gel); EI-HRMS m/e calcd for C20H22N4O3S (M+) 398.1413, found 398.1413.

Workup

  1. customThe resulting reaction mixture
  2. temperatureto warm to 25° C. where it
  3. concentrationThe reaction mixture was then concentrated in vacuo
  4. additionThe resulting yellow gel was diluted with methylene chloride (2 mL)
  5. customThe resulting reaction mixture
  6. stirringwas stirred at 25° C. for 24 h
  7. customThe layers were separated
  8. dry with materialthe organic layer was dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3904c0bc9ee4423fb10e47ebb36b15bf
Source dataset
uspto-grants-2007_05
Patent number
US07223868B2

Reaction notes

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