Hydrochloric 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 445964Notes

Reaction equation

HRID 445964 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].Cl.C([O-])(O)=O.[Na+]>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 5

HCID 313Hydrochloric AcidHCID 6395Methanesulfonic AcidHCID 516892Sodium BicarbonateHCID 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 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-12.5 °C

Procedure

In a 500 mL round bottom flask dry THF (112 mL) and NaBH4 (2.81 g) were taken. It was cooled to −15 to −10° C. After that methanesulfonic acid (17.7 g) was added dropwise at −15 to −5° C. over a period of 1.5 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) was mixed in a solvent mixture of dry THF (25 mL) and IPA (11 mL) and added into the reaction mixture over a period of 45-60 min. at −10 to −5. It was stirred for 30-60 min. at −10 to −5° C. Reaction mixture was poured into cold 10% aq. HCl solution. It was basified by adding aq. NaHCO3 solution. Product was extracted in ethyl acetate. The organic layer was collected, washed with water and brine solution. It was dried over anhydrous sodium sulfate. Solvent was evaporated at reduced pressure to obtain the product. (Wt.-12.4 g, % Purity by HPLC-94.9%).

Workup

  1. additionadded into the reaction mixture over a period of 45-60 min. at −10 to −5
  2. customReaction mixture
  3. extractionProduct was extracted in ethyl acetate
  4. customThe organic layer was collected
  5. washwashed with water and brine solution
  6. dry with materialIt was dried over anhydrous sodium sulfate
  7. customSolvent was evaporated at reduced pressure
  8. customto obtain the product

Sources & evidence

ORD record
ord-5b8cb780d26b489185301d29b7d4f49a
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Reaction notes

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