Ammonia → 3-Amino-1-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo(4,3-a)pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one

HRID 445957Notes

Reaction equation

HRID 445957 reaction equation
CS(O)(=O)=O.[O:6]=[C:7]([N:21]1[CH2:26][CH2:25][N:24]2[C:27]([C:30]([F:33])([F:32])[F:31])=[N:28][N:29]=[C:23]2[CH2:22]1)[CH:8]=[C:9]([NH2:20])[CH2:10][C:11]1[CH:16]=[C:15]([F:17])[C:14]([F:18])=[CH:13][C:12]=1[F:19].CC(O)C.N>C1COCC1.O>[O:6]=[C:7]([N:21]1[CH2:26][CH2:25][N:24]2[C:27]([C:30]([F:33])([F:32])[F:31])=[N:28][N:29]=[C:23]2[CH2:22]1)[CH2:8][CH:9]([NH2:20])[CH2:10][C:11]1[CH:16]=[C:15]([F:17])[C:14]([F:18])=[CH:13][C:12]=1[F:19]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 3776IsopropanolHCID 6395Methanesulfonic AcidHCID 534002733-Amino-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-2-en-1-one

Product 1

HCID 113066913-Amino-1-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo(4,3-a)pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-10 °C

Procedure

In a 50 mL round bottom flask dry THF (17 mL) was taken. It was cooled to −10° C. and 2.0 M Borane methyl sulfide complex solutions in THF (7.41 mL) were added. After that methanesulfonic acid (2.4 mL) was added dropwise at −10° C. over a period of 15-30 min. 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine (2.0 g) is mixed in a solvent mixture of THF (5.0 mL) and IPA (5.0 mL) and added into the reaction mixture, keeping the temperature between −10 to −5. It was stirred for 4 h at −10 to −5° C. Reaction mixture was poured into cold water. It was basified by adding aq. ammonia solution. Product was extracted in ethyl acetate. The organic layer was collected, was washed with water and dried over anhydrous sodium sulfate. Solvent was evaporated at reduced pressure to obtain the product. (Wt.-2.0 g, % Y-100%, % H2O-5.18%, % Purity by HPLC-96.6%). XRD-amorphous-FIG. 1

Workup

  1. additionadded into the reaction mixture
  2. customReaction mixture
  3. extractionProduct was extracted in ethyl acetate
  4. customThe organic layer was collected
  5. washwas washed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. customSolvent was evaporated at reduced pressure
  8. customto obtain the product

Sources & evidence

ORD record
ord-05b8db38083942b0843a781b95935868
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Reaction notes

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