2-(Chloromethyl)-4-isopropyl-6-methoxybenzo[D]isothiazol-3(2H)-one 1,1-dioxide → 2-[3-(4-morpholinylmethyl)-4-oxo-4-H-pyrido[1,2-a]pyrimidin-2yl]oxymethyl-4-isopropyl-6-methoxysaccharin

HRID 1768714Notes

Reaction equation

HRID 1768714 reaction equation
Cl.[N:2]1([CH2:8][CH:9]2[C:14](=[O:15])[N:13]3[CH:16]=[CH:17][CH:18]=[CH:19][C:12]3=[N:11][C:10]2=[O:20])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.CC(C)([O-])C.[K+].Cl[CH2:28][N:29]1[C:39](=[O:40])[C:38]2[C:33](=[CH:34][C:35]([O:44][CH3:45])=[CH:36][C:37]=2[CH:41]([CH3:43])[CH3:42])[S:30]1(=[O:32])=[O:31]>CN(C)C=O.O>[N:2]1([CH2:8][C:9]2[C:14](=[O:15])[N:13]3[CH:16]=[CH:17][CH:18]=[CH:19][C:12]3=[N:11][C:10]=2[O:20][CH2:28][N:29]2[C:39](=[O:40])[C:38]3[C:33](=[CH:34][C:35]([O:44][CH3:45])=[CH:36][C:37]=3[CH:41]([CH3:43])[CH3:42])[S:30]2(=[O:31])=[O:32])[CH2:3][CH2:4][O:5][CH2:6][CH2:7]1

Participants

6

Reactant 3

HCID 99951732-(Chloromethyl)-4-isopropyl-6-methoxybenzo[D]isothiazol-3(2H)-one 1,1-dioxideHCID 19373059HCID 19373059, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 152931482-[3-(4-morpholinylmethyl)-4-oxo-4-H-pyrido[1,2-a]pyrimidin-2yl]oxymethyl-4-isopropyl-6-methoxysaccharinYield 47.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(4-morpholinylmethyl)pyrido[1,2-a]pyrimidine-2,4-dione hydrochloride (0.6 g) and potassium t-butoxide (0.49 g) in dimethylformamide (20 mL) was stirred at room temperature for five minutes. 2-Chloromethyl-4-isopropyl-6-methoxysaccharin (0.61 g) was added and stirring was continued at room temperature for one hour. The reaction mixture was diluted with water (50 mL) and extracted with dichlormethane (3×200 mL). The dichloromethane extract was dried over sodium sulfate and stripped of volatiles, finally under high vacuum. The crude product (780 mg) was combined with that (0.65 g) from another run at the same scale using sodium hydride (60% dispersion in mineral oil, 0.19 g) instead of potassium t-butoxide and purified by column chromatography on silica gel with dichloromethane-methanol (95:5) as eluant affording 2-[3-(4-morpholinylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl]oxymethyl-4-isopropyl-6-methoxysaccharin (500 mg, 23% yield), part of which was recrystallized from ethanol (m.r. 177°-180 ° C.).

Workup

  1. stirringstirring
  2. waitwas continued at room temperature for one hour
  3. extractionextracted with dichlormethane (3×200 mL)
  4. extractionThe dichloromethane extract
  5. dry with materialwas dried over sodium sulfate
  6. custompurified by column chromatography on silica gel with dichloromethane-methanol (95:5) as eluant

Sources & evidence

ORD record
ord-3ca79a10cdd143a08101306417ee2fed
Source dataset
uspto-grants-1995_01
Patent number
US05378720

Reaction notes

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