Alpha-chlorobenzaldoxime → 5-(4-(Isopropylsulfonyl)phenyl)-3-(3-phenyl-4,5-dihydroisoxazol-5-yl)pyrazin-2-amine

HRID 78691Notes

Reaction equation

HRID 78691 reaction equation
[CH:1]([S:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([CH:20]=[CH2:21])[C:16]([NH2:19])=[N:17][CH:18]=2)=[CH:9][CH:8]=1)(=[O:6])=[O:5])([CH3:3])[CH3:2].[OH:22]/[N:23]=[C:24](\Cl)/[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C)C=O.C(OCC)(=O)C.O>[CH:1]([S:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([CH:20]3[O:22][N:23]=[C:24]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:21]3)[C:16]([NH2:19])=[N:17][CH:18]=2)=[CH:9][CH:8]=1)(=[O:5])=[O:6])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 5706359Alpha-chlorobenzaldoximeHCID 866827695-(4-(Isopropylsulfonyl)phenyl)-3-vinylpyrazin-2-amine

Product 1

HCID 715219955-(4-(Isopropylsulfonyl)phenyl)-3-(3-phenyl-4,5-dihydroisoxazol-5-yl)pyrazin-2-amineYield 29%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To solution of 5-(4-isopropylsulfonylphenyl)-3-vinyl-pyrazin-2-amine (20 mg, 0.06592 mmol) in N,N-dimethylformamide (2 mL) was added (Z)—N-hydroxybenzimidoyl chloride (13.33 mg, 0.08570 mmol) followed by TEA (20.02 mg, 27.58 μL, 0.1978 mmol) added drop wise. The reaction mixture was stirred at ambient temperature for 20 mins followed by heating to 65° C. for 1 hour. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (5 mL) and water (5 mL) and the layers separated. The aqueous layer was extracted further with ethyl acetate (2×5 mL) and the combined organic extracts washed with water (3×10 mL), dried over MgSO4 and concentrated in vacuo to a solid. Purification by fractionlynx yielded 5-(4-(isopropylsulfonyl)phenyl)-3-(3-phenyl-4,5-dihydroisoxazol-5-yl)pyrazin-2-amine Compound I-1. (10.4 mg, 29% Yield). DMSO 1.15 (6H,d), 3.4-3.48 (1H,m) 3.7-3.8 (1H,m), 4.28 (1H,dd), 6.02 (1H,dd), 6.95 (2H,brs), 7.48-7.53 (3H,m), 7.78-7.85 (4H,m), 8.2 (2H,d), 8.75 (1H,s); LC/MS m/z 423.4 [M+H]+.

Workup

  1. additionadded drop wise
  2. temperatureby heating to 65° C. for 1 hour
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted further with ethyl acetate (2×5 mL)
  6. washthe combined organic extracts washed with water (3×10 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo to a solid
  9. customPurification by fractionlynx

Sources & evidence

ORD record
ord-7c6cea91e3d84b388426a5c424f71d9e
Source dataset
uspto-grants-2014_09
Patent number
US08841450B2

Reaction notes

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