2,2,2-Trifluoroethanol → N-(3-((2-chloro-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)-N-methylmethanesulfonamide

HRID 886998Notes

Reaction equation

HRID 886998 reaction equation
C(O)(=O)C.[NH2:5][CH2:6][C:7]1[C:8]([N:13]([CH3:18])[S:14]([CH3:17])(=[O:16])=[O:15])=[N:9][CH:10]=[CH:11][CH:12]=1.C(O)C(F)(F)F.[Cl:25][C:26]1[N:31]=[C:30](Cl)[C:29]([C:33]([F:36])([F:35])[F:34])=[CH:28][N:27]=1>C(N(CC)CC)C>[Cl:25][C:26]1[N:27]=[C:28]([NH:5][CH2:6][C:7]2[C:8]([N:13]([CH3:18])[S:14]([CH3:17])(=[O:16])=[O:15])=[N:9][CH:10]=[CH:11][CH:12]=2)[C:29]([C:33]([F:36])([F:34])[F:35])=[CH:30][N:31]=1

Participants

5

Reactant 3

HCID 64092,2,2-Trifluoroethanol2×HCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidine2×HCID 67099950N-(3-(Aminomethyl)pyridin-2-yl)-N-methylmethanesulfonamide acetate2×

Product 1

HCID 57584561N-(3-((2-chloro-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)-N-methylmethanesulfonamide

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
25 °C

Procedure

A solution of B5 and trifluoroethanol (120 mL) was treated with triethylamine (TEA) (16.6 mL) and stirred at 25° C. for 1 hour. In a separate reaction flask, a solution of 2,4-dichloro-5-trifluoromethylpyrimidine (13.2 g, 60.8 mmol) and trifluoroethanol (120 mL) was cooled to −45° C. The cold 2,4-dichloro-5-trifluoromethylpyrimidine solution was then treated drop-wise with the solution containing B5 and stirred at −45° C. for 2 hours. The mixture was allowed to warm to 25° C., and it was stirred at 25° C. for about 20 hours. The reaction mixture was then concentrated and cooled to 0° C. The resultant white mixture was diluted with EtOAc (15 ml), and the solids collected by filtration. The white solids were then washed with water and EtOAc to provide C9. Yield: 0.7 g, 45%. 1H NMR (400 MHz, d6-DMSO) δ: 3.07 (s, 3H), 3.29(s, 3H), 4.68 (d, 2H), 7.39 (m, 1H), 7.72 (d, 1H), 8.40 (s, 1H), 8.50 (t, 1H); ESI-MS: 396.0 (MH+).

Workup

  1. customIn a separate reaction flask
  2. stirringstirred at −45° C. for 2 hours
  3. temperatureto warm to 25° C.
  4. stirringit was stirred at 25° C. for about 20 hours
  5. concentrationThe reaction mixture was then concentrated
  6. temperaturecooled to 0° C
  7. additionThe resultant white mixture was diluted with EtOAc (15 ml)
  8. filtrationthe solids collected by filtration
  9. washThe white solids were then washed with water and EtOAc

Sources & evidence

ORD record
ord-e877ff4c8a1d48058de5985ba7d0e896
Source dataset
uspto-grants-2012_08
Patent number
US08247411B2

Reaction notes

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