Pyridine → HCID 59253295, compound

HRID 386913Notes

Reaction equation

HRID 386913 reaction equation
[CH3:1][O:2][C:3]1[CH:34]=[CH:33][C:6]([CH2:7][NH:8][CH2:9][C:10]([C:13]2[CH:17]=[C:16]([NH:18][C:19](=[O:32])[C:20]([CH3:31])([S:22]([CH:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)(=[O:24])=[O:23])[CH3:21])[O:15][N:14]=2)([CH3:12])[CH3:11])=[CH:5][CH:4]=1.N1C=CC=CC=1.[C:41](Cl)(=[O:43])[CH3:42]>C1COCC1>[C:41]([N:8]([CH2:7][C:6]1[CH:33]=[CH:34][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[CH2:9][C:10]([C:13]1[CH:17]=[C:16]([NH:18][C:19](=[O:32])[C:20]([CH3:21])([S:22]([CH:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)(=[O:24])=[O:23])[CH3:31])[O:15][N:14]=1)([CH3:12])[CH3:11])(=[O:43])[CH3:42]

Participants

5

Reactant 3

HCID 1049Pyridine2×HCID 6367Acetyl chloride2×HCID 59253151HCID 59253151, compound

Product 1

HCID 59253295HCID 59253295, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-{3-[2-(4-methoxy-benzylamino)-1,1-dimethyl-ethyl]-isoxazol-5-yl}-2-methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionamide (143 mg, 0.29 mmol) in THF (1.5 mL) are added pyridine (0.035 mL, 0.44 mmol) and acetyl chloride (0.031 mL, 0.44 mmol). The reaction mixture is stirred at room temperature for 3.5 h. After this time, more pyridine (0.018 mL, 0.22 mmol) and acetyl chloride (0.016 mL, 0.22 mmol) are added to the reaction mixture and the stirring is continued for 1 h. After this time, the reaction mixture is quenched with saturated aqueous NaHCO3 solution and extracted with ethyl acetate twice. The organic extracts are combined and washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel using methanol/DCM provides the title compound. Yield: 75%; LC-MS retention time: 1.62 mins. ESI+ion mode. Zorbax SB-C18 column (3.5 μm, 4.6×30 mm). Gradient: 5% B to 80% B (0 min to 1.7 mins), 80% B to 95% B (1.7 mins to 2 mins), 95% B to 95% B (2 mins to 2.1 mins). Flow rate: 2.5 mL/min. A=(Water+0.1% Formic Acid), B=(Acetonitrile+0.1% Formic Acid). Diode Array Detector; m/z 536 [M+H].

Workup

  1. waitthe stirring is continued for 1 h
  2. customAfter this time, the reaction mixture is quenched with saturated aqueous NaHCO3 solution
  3. extractionextracted with ethyl acetate twice
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-dc11396568c149af9fc048057efe76ce
Source dataset
uspto-grants-2013_02
Patent number
US08372874B2

Reaction notes

Loading…