1,4-Dioxane → 5-(morpholin-4-ylcarbonyl)-4-(trifluoromethyl)-N-[(1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]pyrimidin-2-amine

HRID 38779Notes

Reaction equation

HRID 38779 reaction equation
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][O:17][CH2:16][CH2:15]2)=[O:13])=[CH:4][N:3]=1.[CH3:20][C@:21]12[C:27]([CH3:29])([CH3:28])[C@H:24]([CH2:25][CH2:26]1)[CH2:23][C@@H:22]2[NH2:30].O1CCOCC1>O>[N:14]1([C:12]([C:5]2[C:6]([C:8]([F:11])([F:10])[F:9])=[N:7][C:2]([NH:30][C@H:22]3[CH2:23][C@@H:24]4[C:27]([CH3:29])([CH3:28])[C@@:21]3([CH3:20])[CH2:26][CH2:25]4)=[N:3][CH:4]=2)=[O:13])[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 6553267(R)-(+)-BornylamineHCID 581687074-{[2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}morpholine

Product 1

HCID 667201455-(morpholin-4-ylcarbonyl)-4-(trifluoromethyl)-N-[(1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]pyrimidin-2-amineYield 70.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4-{[2-chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}morpholine (100 mg), (1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-amine (207 mg), and 1,4-dioxane (2 mL) was stirred at room temperature for 3 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, 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), and the obtained colorless oily substance was solidified from hexane-ethyl acetate to obtain 5-(morpholin-4-ylcarbonyl)-4-(trifluoromethyl)-N-[(1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]pyrimidin-2-amine (98 mg) as a white solid.

Workup

  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. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)

Sources & evidence

ORD record
ord-983dc49c26ca4b07875a2a4a77273c02
Source dataset
uspto-grants-2013_09
Patent number
US08524727B2

Reaction notes

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