Morpholine → rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-5-(morpholin-4-ylmethyl)-4-(trifluoromethyl)pyrimidin-2-amine hydrochloride

HRID 38784ノート

反応式

HRID 38784 の反応式
[C@H:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[CH2:3][C@H:2]2[NH:8][C:9]1[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]([CH2:19][Cl:20])=[CH:11][N:10]=1.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1>CN(C)C=O>[ClH:20].[C@H:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[CH2:3][C@H:2]2[NH:8][C:9]1[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]([CH2:19][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:11][N:10]=1

参加物

4

反応物 2

HCID 8083MorpholineHCID 66720336rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-5-(chloromethyl)-4-(trifluoromethyl)pyrimidin-2-amine

生成物 1

HCID 66720216rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-5-(morpholin-4-ylmethyl)-4-(trifluoromethyl)pyrimidin-2-amine hydrochloride

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-5-(chloromethyl)-4-(trifluoromethyl)pyrimidin-2-amine (200 mg) and N,N-dimethyl formamide (3 mL) was added morpholine (0.57 mL), and the mixture was stirred at room temperature for 15 hours. The solvent was evaporated under reduced pressure from the reaction mixture, and water was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate). The obtained colorless oil was dissolved in 1,4-dioxane (5 mL), and a 4 M hydrogen chloride/1,4-dioxane solution (1 mL) was added thereto, followed by stirring at room temperature for 1 hour. The precipitated solid was collected by filtration and washed with 1,4-dioxane to obtain rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-5-(morpholin-4-ylmethyl)-4-(trifluoromethyl)pyrimidin-2-amine hydrochloride (187 mg) as a white solid.

後処理

  1. customThe solvent was evaporated under reduced pressure from the reaction mixture, and water
  2. additionwas added to the residue
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)
  8. dissolutionThe obtained colorless oil was dissolved in 1,4-dioxane (5 mL)
  9. additiona 4 M hydrogen chloride/1,4-dioxane solution (1 mL) was added
  10. stirringby stirring at room temperature for 1 hour
  11. filtrationThe precipitated solid was collected by filtration
  12. washwashed with 1,4-dioxane

出典と根拠

ORDレコード
ord-6785173f8662418c90b548979491a876
出典データセット
uspto-grants-2013_09
特許番号
US08524727B2

反応ノート

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