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 445955Notes

Reaction equation

HRID 445955 reaction equation
[BH4-].[Na+].CS(O)(=O)=O.[O:8]=[C:9]([N:23]1[CH2:28][CH2:27][N:26]2[C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][N:31]=[C:25]2[CH2:24]1)[CH:10]=[C:11]([NH2:22])[CH2:12][C:13]1[CH:18]=[C:17]([F:19])[C:16]([F:20])=[CH:15][C:14]=1[F:21].N>O.CC(O)C.C1COCC1>[O:8]=[C:9]([N:23]1[CH2:28][CH2:27][N:26]2[C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][N:31]=[C:25]2[CH2:24]1)[CH2:10][CH:11]([NH2:22])[CH2:12][C:13]1[CH:18]=[C:17]([F:19])[C:16]([F:20])=[CH:15][C:14]=1[F:21]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 6395Methanesulfonic AcidHCID 4311764Sodium borohydrideHCID 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 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-12.5 °C

Procedure

In a 250 mL round bottom flask THF (75 mL) was taken. It was cooled to −15 to −10° C. and NaBH4 (1.87 g) was added. After that methanesulfonic acid (11.8 g) was added dropwise at −15 to −10° C. over a period of 30-45 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 (10.0 g) is mixed in a solvent mixture of THF and IPA and added into the reaction mixture, keeping the temperature −10 to −5° C. It was stirred for 30-60 min. 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. It was washed with water and dried over anhydrous sodium sulfate. Solvent was evaporated at reduced pressure to obtain the product. (Wt.-9.15 g; % Y-91%; % Purity by HPLC-88.6%).

Workup

  1. additionadded into the reaction mixture
  2. customthe temperature −10 to −5° C
  3. customReaction mixture
  4. extractionProduct was extracted in ethyl acetate
  5. customThe organic layer was collected
  6. washIt was washed with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. customSolvent was evaporated at reduced pressure
  9. customto obtain the product

Sources & evidence

ORD record
ord-26b817f8143740e089f0a613e42f282c
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Reaction notes

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