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 445954Notes

Reaction equation

HRID 445954 reaction equation
C1COCC1.[BH4-].[Na+].CS(O)(=O)=O.[O:13]=[C:14]([N:28]1[CH2:33][CH2:32][N:31]2[C:34]([C:37]([F:40])([F:39])[F:38])=[N:35][N:36]=[C:30]2[CH2:29]1)[CH:15]=[C:16]([NH2:27])[CH2:17][C:18]1[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=1[F:26]>CC(O)C>[O:13]=[C:14]([N:28]1[CH2:33][CH2:32][N:31]2[C:34]([C:37]([F:40])([F:39])[F:38])=[N:35][N:36]=[C:30]2[CH2:29]1)[CH2:15][CH:16]([NH2:27])[CH2:17][C:18]1[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=1[F:26]

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 8028Tetrahydrofuran2×HCID 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 1

HCID 3776IsopropanolSolvent

Procedure

In a 250 mL round bottom flask THF (110 mL) was taken. It was cooled to less than −5° C. and NaBH4 (2.81 g) was added. After that methanesulfonic acid (17.8 g) was added dropwise at less than −5° C. over a period of 1 h. 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 (25 mL) and IPA (11 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.-9.5 g, % Y-94.5%, % Purity by HPLC-94.6%).

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-e53c121a5ef34ef1887be4290aca41fd
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Reaction notes

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