Ethanesulfonyl chloride → (S)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-7-(ethylsulfonyl)-3-phenyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide

HRID 1971083Notes

Reaction equation

HRID 1971083 reaction equation
[CH3:1][C:2]([CH3:27])([CH3:26])[C@H:3]([NH:8][C:9]([C:11]1[N:12]=[C:13]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:14]2[CH2:19][CH2:18][NH:17][CH2:16][C:15]=12)=[O:10])[C:4]([NH:6][CH3:7])=[O:5].[CH2:28]([S:30](Cl)(=[O:32])=[O:31])[CH3:29].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:1][C:2]([CH3:27])([CH3:26])[C@H:3]([NH:8][C:9]([C:11]1[N:12]=[C:13]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:14]2[CH2:19][CH2:18][N:17]([S:30]([CH2:28][CH3:29])(=[O:32])=[O:31])[CH2:16][C:15]=12)=[O:10])[C:4]([NH:6][CH3:7])=[O:5]

Participants

5

Reactant 3

HCID 11667Ethanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 25132789(S)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-3-phenyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide

Product 1

HCID 25129721(S)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-7-(ethylsulfonyl)-3-phenyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamideYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Compound 2 (150 mg, 0.41 mmol) was dissolved in DCM and cooled to 0° C. Ethanesulfonyl chloride (62.2 mg, 0.49 mmol) was added, followed by DIEA (0.21 mL, 1.22 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred overnight. The mixture was diluted with DCM and washed with saturated NaHCO3 solution. The organic layer was separated, washed with brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by normal phase chromatography eluting with 10-50% methanol/DCM gradient to provide Compound 91 as a white solid (0.13 g, 69%). MS: m/z 462.34 [M+H]+.

Workup

  1. temperatureto warm to ambient temperature
  2. washwashed with saturated NaHCO3 solution
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by normal phase chromatography
  8. washeluting with 10-50% methanol/DCM gradient

Sources & evidence

ORD record
ord-1426660cee4b4fd58f2ecf7951ad223b
Source dataset
uspto-grants-2013_04
Patent number
US08431565B2

Reaction notes

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