Dimethylformamide → 3-[5-[3-[(Dimethylamino)methyl]phenyl]-1,3,4-oxadiazol-2-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine

HRID 78637Notes

Reaction equation

HRID 78637 reaction equation
NC[C:3]1[CH:4]=[C:5]([C:9]2[O:13][C:12]([C:14]3[C:15]([NH2:32])=[N:16][CH:17]=[C:18]([C:20]4[CH:25]=[CH:24][C:23]([S:26]([CH:29]([CH3:31])[CH3:30])(=[O:28])=[O:27])=[CH:22][CH:21]=4)[N:19]=3)=[N:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1.CI.C(=O)([O-])[O-].[K+].[K+].[CH3:41][N:42]([CH:44]=O)[CH3:43]>C(OCC)(=O)C>[CH3:43][N:42]([CH2:44][C:3]1[CH:4]=[C:5]([C:9]2[O:13][C:12]([C:14]3[C:15]([NH2:32])=[N:16][CH:17]=[C:18]([C:20]4[CH:25]=[CH:24][C:23]([S:26]([CH:29]([CH3:30])[CH3:31])(=[O:27])=[O:28])=[CH:22][CH:21]=4)[N:19]=3)=[N:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1)[CH3:41]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 594716333-[5-[3-(Aminomethyl)phenyl]-1,3,4-oxadiazol-2-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-amine

Product 1

HCID 594722773-[5-[3-[(Dimethylamino)methyl]phenyl]-1,3,4-oxadiazol-2-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amineYield 24%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

3-[5-[3-(aminomethyl)phenyl]-1,3,4-oxadiazol-2-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-amine (12 mg, 0.02108 mmol) was added to a solution of MeI (8.976 mg, 3.937 μL, 0.06324 mmol) and potassium carbonate (8.740 mg, 0.06324 mmol) in DMF (2 mL). The resulting mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate (3 mL) and washed successively with water (1×5 mL) and brine (1×5 mL). The organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. Product fractions were combined and lypholised to give the product as a yellow solid (3.0 mg, 24% yield); 1H NMR (400 MHz, MeOD) d 1.35-1.4 (m, 6H), 2.95 (s, 6H), 4.65 (s, 2H), 7.8-7.85 (m, 2H), 8.05-8.1 (m, 2H), 8.4-8.5 (m, 4H) and 9.95 (s, 1H) ppm; MS (ES+) 479.3

Workup

  1. washwashed successively with water (1×5 mL) and brine (1×5 mL)
  2. dry with materialThe organic extracts were dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]

Sources & evidence

ORD record
ord-9d7a1f4e61844efbbc9b5ee3af99e166
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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