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

HRID 38804

反応式

HRID 38804 の反応式
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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418751HCID 178418751、化合物触媒HCID 962Water溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-ee3956ee1d6c4d3aba3a6a9f19e5276b
出典データセット
uspto-grants-2013_09
特許番号
US08524727B2

関連ノート

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