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

HRID 38784Notes

Reaction equation

HRID 38784 reaction equation
[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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-6785173f8662418c90b548979491a876
Source dataset
uspto-grants-2013_09
Patent number
US08524727B2

Reaction notes

Loading…