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 → (3S)-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 445971Notes

Reaction equation

HRID 445971 reaction equation
O.C([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.[O:28]=[C:29]([N:43]1[CH2:48][CH2:47][N:46]2[C:49]([C:52]([F:55])([F:54])[F:53])=[N:50][N:51]=[C:45]2[CH2:44]1)[CH2:30][CH:31]([NH2:42])[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41]>CCO>[O:28]=[C:29]([N:43]1[CH2:48][CH2:47][N:46]2[C:49]([C:52]([F:55])([F:54])[F:53])=[N:50][N:51]=[C:45]2[CH2:44]1)[CH2:30][C@@H:31]([NH2:42])[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41]

Participants

4

Reactant 2

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-oneHCID 130366077Dibezoyl-L-tartaric acid monohydrate

Product 1

HCID 11432118(3S)-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-oneYield 20.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
62.5 °C

Procedure

In a 50 mL three neck flask EtOH (5 mL) and Dibenzoyl-L-tartaric acid monohydrate (1.84 g) were taken. It was heated to 60-65° C. 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (2.0 g, % purity-93.8%) dissolved in EtOH (6 mL) was added into reaction mixture at 60-65° C. It was stirred for 1 h at 60-65° C. Solid salt was precipitated. It was gradually cooled to room temperature over a period of 2-3 h. The salt was filtered and washed with cold EtOH. An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of mixture of (2R) and (2S)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine was obtained (Wt.-0.8 g, yield-20.9%, Purity by HPLC-99.6%, % Chiral purity by HPLC of R-isomer 78%).

Workup

  1. additionwas added into reaction mixture at 60-65° C
  2. customSolid salt was precipitated
  3. temperatureIt was gradually cooled to room temperature over a period of 2-3 h
  4. filtrationThe salt was filtered
  5. washwashed with cold EtOH
  6. additionAn enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of mixture of (2R)

Sources & evidence

ORD record
ord-0e347fe5da054531a37a68c311b22128
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Reaction notes

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