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 445965Notes

Reaction equation

HRID 445965 reaction equation
[BH4-].[Na+].B(F)(F)F.CCOCC.[O:12]=[C:13]([N:27]1[CH2:32][CH2:31][N:30]2[C:33]([C:36]([F:39])([F:38])[F:37])=[N:34][N:35]=[C:29]2[CH2:28]1)[CH:14]=[C:15]([NH2:26])[CH2:16][C:17]1[CH:22]=[C:21]([F:23])[C:20]([F:24])=[CH:19][C:18]=1[F:25].N>O.CC(O)C.C1COCC1>[O:12]=[C:13]([N:27]1[CH2:32][CH2:31][N:30]2[C:33]([C:36]([F:39])([F:38])[F:37])=[N:34][N:35]=[C:29]2[CH2:28]1)[CH2:14][CH:15]([NH2:26])[CH2:16][C:17]1[CH:22]=[C:21]([F:23])[C:20]([F:24])=[CH:19][C:18]=1[F:25]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 8000Boron trifluoride etherateHCID 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 100 mL round bottom flask dry THF (50 mL) was taken. It was cooled to −15 to −10° C. and NaBH4 (1.1 g) was added. After that boron trifluoride etherate (10.9 g) was added dropwise at −15 to −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 (5.0 g) was mixed in a solvent mixture of dry THF (12.5 mL) and IPA (5.5 mL) and added into the reaction mixture over a period of 45-60 min. at −10 to −5° C. It was stirred for 2.5 h 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 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.-4.81 g, % Y-95.8%, % Purity by HPLC-96.5%).

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 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-e77315f0d4b3480cb9b94a7af2be0499
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Reaction notes

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