Tetrahydrofuran → 4-{[2-(3-Chlorobenzyl)-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}thiomorpholine 1,1-dioxide

HRID 38804

반응식

HRID 38804 반응식
Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12]([N:14]2[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16][CH2:15]2)=[O:13])=[CH:4][N:3]=1.O1CCCC1.O1CCCC1.Cl[Zn][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[CH:36]=1>Cl[Ni](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Cl:41][C:37]1[CH:36]=[C:35]([CH:40]=[CH:39][CH:38]=1)[CH2:34][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12]([N:14]2[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16][CH2:15]2)=[O:13])=[CH:4][N:3]=1

참가 물질

6

반응물 3

HCID 8028TetrahydrofuranHCID 581689914-{[2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}thiomorpholine 1,1-dioxideHCID 178420685HCID 178420685, 화합물

생성물 1

HCID 667201394-{[2-(3-Chlorobenzyl)-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}thiomorpholine 1,1-dioxide

시약·촉매·용매 2

HCID 178418751HCID 178418751, 화합물촉매HCID 962Water용매

실험 절차

To a mixture of 4-{[2-chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}thiomorpholine 1,1-dioxide (500 mg), dichlorobis(triphenylphosphine)nickel (II) (190 mg), tetrahydrofuran (10 mL) was added a 0.5 M chloro(3-chlorobenzyl)zinc tetrahydrofuran solution (3.2 mL), followed by stirring at room temperature for 6 hours. To the reaction mixture was added water and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, then dried over anhydrous magnesium sulfate, filtered, and concentrated. The obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate). To the obtained pale yellow solid were added 1,4-dioxane (10 mL) and 1-methylpiperazine (0.16 mL), followed by stirring at room temperature for 6 hours. To the reaction mixture was added water and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, then dried over anhydrous magnesium sulfate, filtered, and concentrated. The obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate). The obtained white solid was washed with ethanol to obtain 4-{[2-(3-chlorobenzyl)-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}thiomorpholine 1,1-dioxide (212 mg) as a white solid.

후처리

  1. extractionthe aqueous layer was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)
  7. additionTo the obtained pale yellow solid were added 1,4-dioxane (10 mL) and 1-methylpiperazine (0.16 mL)
  8. stirringby stirring at room temperature for 6 hours
  9. additionTo the reaction mixture was added water
  10. extractionthe aqueous layer was extracted with ethyl acetate
  11. washThe organic layer was washed with water and saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)
  16. washThe obtained white solid was washed with ethanol

출처 및 근거

ORD 기록
ord-ee3956ee1d6c4d3aba3a6a9f19e5276b
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524727B2

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