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 445956Notes

Reaction equation

HRID 445956 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.[F-].[K+]>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

9

Reactant 5

HCID 222AmmoniaHCID 6395Methanesulfonic AcidHCID 522689Potassium FluorideHCID 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 962WaterSolvent2×HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-12.5 °C

Procedure

In a 2 L round bottom flask dry THF (450 mL) was taken. It was cooled to −15 to −10° C. and NaBH4 (11.2 g) was added. After that methanesulfonic acid (71.1 g) was added dropwise at −15 to −5° C. over a period of 2.5 h. Separately, 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 (40.0 g) was mixed in a solvent mixture of dry THF (100 mL) and IPA (44 mL) and added into the reaction mixture over a period of 45-60 min. at −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 25% aq. ammonia solution. Product was extracted in an ethyl acetate. The organic layer was collected and combined. It was washed with water and brine solution. It was dried over anhydrous sodium sulfate. Solvent was evaporated at reduced pressure to obtain the product. (Wt.-41.5 g; % Y-100%; % Purity by HPLC-94.5%; % H2O by KF-4.58%).

Workup

  1. additionadded into the reaction mixture over a period of 45-60 min. at −10 to −5° C
  2. customReaction mixture
  3. extractionProduct was extracted in an ethyl acetate
  4. customThe organic layer was collected
  5. washIt was washed 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-843e330e846b4a919c7996c8189893fa
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Reaction notes

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