Water → 5-chloro-6-(2,4,6-trifluorophenyl)-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine

HRID 747098

Reaction equation

HRID 747098 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[C:13]([F:14])=[CH:12][C:11]([F:15])=[CH:10][C:9]=2[F:16])=[C:6](Cl)[N:5]2[N:18]=[CH:19][N:20]=[C:4]2[N:3]=1.[F:21][C:22]([F:27])([F:26])[C@@H:23]([NH2:25])[CH3:24].O>CN(C=O)C>[Cl:1][C:2]1[C:7]([C:8]2[C:13]([F:14])=[CH:12][C:11]([F:15])=[CH:10][C:9]=2[F:16])=[C:6]([NH:25][C@@H:23]([CH3:24])[C:22]([F:27])([F:26])[F:21])[N:5]2[N:18]=[CH:19][N:20]=[C:4]2[N:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 10964447(S)-1,1,1-trifluoropropan-2-amineHCID 110453875,7-Dichloro-6-(2,4,6-trifluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine

Product 1

HCID 119750435-chloro-6-(2,4,6-trifluorophenyl)-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5,7-dichloro-6-(2,4,6-trifluorophenyl)-[1,2,4]triazolo[1,5-a]-pyrimidine (200 g, 0.627 mol) in anhydrous DMF (1000 mL) is added (S)-2,2,2-trifluoro-1-methyl-ethylamine (177 g, 1.57 mol). The solution is stirred from about 20° C. to about 30° C. for 24 h. The reaction mixture is added to cold water (3000 mL) slowly over 30 min. The mixture is stirred for 30 min at 10-20° C. The solid product is filtered and washed with water (2×500 mL). The crude product is dissolved into IPA (1000 mL) at 50° C. Water (2000 mL) is added to precipitate the product over 30 min. The mixture is cooled to 0° C. over 1 h and stirred for 1 h at this temperature. The solid is filtered and dried at 65° C./10 mmHg for 20 h to give a light yellow solid (204 g, 82%, 98% HPLC area purity and 99% ee).

Workup

  1. stirringThe mixture is stirred for 30 min at 10-20° C
  2. filtrationThe solid product is filtered
  3. washwashed with water (2×500 mL)
  4. dissolutionThe crude product is dissolved into IPA (1000 mL) at 50° C
  5. additionWater (2000 mL) is added
  6. customto precipitate the product over 30 min
  7. stirringstirred for 1 h at this temperature
  8. filtrationThe solid is filtered
  9. customdried at 65° C./10 mmHg for 20 h
  10. customto give a light yellow solid (204 g, 82%, 98% HPLC area purity and 99% ee)

Sources & evidence

ORD record
ord-835e75ffab714e31a6e73f2eec853a59
Source dataset
uspto-grants-2008_07
Patent number
US07396835B2

Linked notes

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