Methanesulfonic Acid → 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 445984Notes

Reaction equation

HRID 445984 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].OC(CC1C=C(F)C(F)=CC=1F)CC(N1CCN2C(C(F)(F)F)=NN=C2C1)=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

7

Reactant 4

HCID 6395Methanesulfonic AcidHCID 4311764Sodium borohydrideHCID 451105493-hydroxy-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-oneHCID 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 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In a 250 mL round bottom flask THF (225 mL) was taken. It was cooled to less than −5° C. and NaBH4 (5.62 g) was added. After that methanesulfonic acid (17.8 g) was added dropwise at less than −5° C. over a period of 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 (20.0 g) is mixed in a solvent mixture of THF (50 mL) and IPA (22 mL) and added into the reaction mixture, keeping the temperature below 0° C. It was stirred for 4-6 h below 5° C. After usual work-up procedure, product was extracted in a suitable solvent. Extract was washed and dried over anhydrous sodium sulfate. Solvent was evaporated at reduced pressure to obtain the product. (Wt.-20.8 g, % Purity by HPLC-80.7% and % of 3-hydroxy-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 by HPLC-15.5%).

Workup

  1. temperatureIt was cooled to less than −5° C.
  2. additionadded into the reaction mixture
  3. customthe temperature below 0° C
  4. extractionAfter usual work-up procedure, product was extracted in a suitable solvent
  5. extractionExtract
  6. washwas washed
  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-15ccc0062cea407e9ab452048ee4494b
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Reaction notes

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