Acetone → HCID 46842202, compound

HRID 445929Notes

Reaction equation

HRID 445929 reaction equation
[SH:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[OH-:11].[Na+].CC(C)=[O:15].Cl[CH2:18][C:19]1[C:20]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)=[N:21][C:22]([N:28]([CH3:33])[S:29]([CH3:32])(=[O:31])=[O:30])=[N:23][C:24]=1[CH:25]([CH3:27])[CH3:26]>O.C(OCC)(=O)C.CCCCCC>[S:3]1[C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=[C:2]1[S:1]([CH2:18][C:19]1[C:20]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)=[N:21][C:22]([N:28]([CH3:33])[S:29]([CH3:32])(=[O:31])=[O:30])=[N:23][C:24]=1[CH:25]([CH3:27])[CH3:26])(=[O:15])=[O:11]

Participants

7

Reactant 4

HCID 180AcetoneHCID 14798Sodium HydroxideHCID 53307901HCID 53307901, compoundHCID 178418395HCID 178418395, compound

Product 1

HCID 46842202HCID 46842202, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

2-Mercaptobenzothiazole (4.1 g) was added to a solution of sodium hydroxide (1.0 g) in water (20.0 mL). The reaction mixture was stirred for 15 minutes, while maintaining the temperature of 25˜35° C. Acetone (36.0 mL) and N-[5-chloromethyl-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-2-yl]-N-methyl-methanesulfonamide (9.0 g) were added to the reaction mixture, which was then stirred for 3 hours, while maintaining the temperature of 25˜35° C. The reaction was monitored with thin layer chromatography (ethyl acetate/n-hexane=1:3). The reaction mixture was cooled to 20˜25° C. and then water (45.0 mL) was added thereto. The separated organic layer was concentrated under reduced pressure to remove the solvent. Dichloromethane (90.0 mL) was added to the resulting residue, which was then cooled to 0˜5° C. m-Chloroperbenzoic acid (13.5 g) was added to the reaction mixture, which was then stirred at 0˜5° C. for 2 hours. The reaction was monitored with thin layer chromatography (ethyl acetate/n-hexane=1:3). The temperature of the reaction mixture was adjusted to 20˜25° C. 10% Sodium sulfite solution (90.0 mL) was added to the reaction mixture under stirring. The separated organic layer was sequentially washed with 8% sodium bicarbonate solution (90.0 mL) and water (90.0 mL), and then concentrated under reduced pressure to remove the solvent. The resulting residue was purified with silica gel column chromatography (ethyl acetate/n-hexane=1:3) to obtain N-[5-benzothiazol-2-sulfonylmethyl-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-2-yl]-N-methyl-methanesulfonamide as a white solid (10.9 g, yield 84%).

Workup

  1. temperaturewhile maintaining the temperature of 25˜35° C
  2. stirringwas then stirred for 3 hours
  3. temperaturewhile maintaining the temperature of 25˜35° C
  4. temperatureThe reaction mixture was cooled to 20˜25° C.
  5. concentrationThe separated organic layer was concentrated under reduced pressure
  6. customto remove the solvent
  7. additionDichloromethane (90.0 mL) was added to the resulting residue, which
  8. temperaturewas then cooled to 0˜5° C. m-Chloroperbenzoic acid (13.5 g)
  9. additionwas added to the reaction mixture, which
  10. stirringwas then stirred at 0˜5° C. for 2 hours
  11. customwas adjusted to 20˜25° C
  12. addition10% Sodium sulfite solution (90.0 mL) was added to the reaction mixture
  13. stirringunder stirring
  14. washThe separated organic layer was sequentially washed with 8% sodium bicarbonate solution (90.0 mL) and water (90.0 mL)
  15. concentrationconcentrated under reduced pressure
  16. customto remove the solvent
  17. customThe resulting residue was purified with silica gel column chromatography (ethyl acetate/n-hexane=1:3)

Sources & evidence

ORD record
ord-16a7be77dde2475a9f01f77b0b488c1c
Source dataset
uspto-grants-2013_07
Patent number
US08476432B2

Reaction notes

Loading…