Methanol → HCID 49801284, compound

HRID 1771517Notes

Reaction equation

HRID 1771517 reaction equation
[H-].[Na+].[CH3:3][OH:4].Cl[CH2:6][C:7]1[CH:12]=[C:11]([C:13]([NH:15][C:16]2[S:17][C:18]([C:26]([CH:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[O:27])=[C:19]([C:21]3[O:22][CH:23]=[CH:24][CH:25]=3)[N:20]=2)=[O:14])[CH:10]=[CH:9][N:8]=1.O>CN(C=O)C>[O:22]1[CH:23]=[CH:24][CH:25]=[C:21]1[C:19]1[N:20]=[C:16]([NH:15][C:13]([C:11]2[CH:10]=[CH:9][N:8]=[C:7]([CH2:6][O:4][CH3:3])[CH:12]=2)=[O:14])[S:17][C:18]=1[C:26]([CH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)=[O:27]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 24758Sodium hydrideHCID 86664359HCID 86664359, compound

Product 1

HCID 49801284HCID 49801284, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Under ice-cooling, 60% sodium hydride (10.0 mg, 0.250 mmol) was dissolved in DMF (1.0 mL), methanol (110 μL, 2.72 mmol) was slowly added dropwise thereto, and the mixture was stirred at 0° C. for 10 min. Then, 2-(chloromethyl)-N-[4-(2-furyl)-5-(tetrahydropyran-4-carbonyl)thiazol-2-yl]pyridine-4-carboxamide (81.0 mg, 0.189 mmol) obtained in step 1 of Reference Example 6, which was dissolved in DMF (1.0 mL), was slowly added dropwise thereto, and the mixture was stirred at room temperature for 5 hr. To the mixture were added water and a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50), and recrystallized from ethanol-water to give compound (IJ) (45.0 mg, 56%) as white crystals.

Workup

  1. temperatureUnder ice-cooling
  2. additionwas slowly added dropwise
  3. stirringthe mixture was stirred at room temperature for 5 hr
  4. extractiona saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50)
  9. customrecrystallized from ethanol-water
  10. customto give compound (IJ) (45.0 mg, 56%) as white crystals

Sources & evidence

ORD record
ord-db18546075854f8e853ebb8934098389
Source dataset
uspto-grants-2016_02
Patent number
US09249135B2

Reaction notes

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