Isopropanol → (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 445969

Reaction equation

HRID 445969 reaction equation
CC(O)C.C([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.[O:31]=[C:32]([N:46]1[CH2:51][CH2:50][N:49]2[C:52]([C:55]([F:58])([F:57])[F:56])=[N:53][N:54]=[C:48]2[CH2:47]1)[CH2:33][CH:34]([NH2:45])[CH2:35][C:36]1[CH:41]=[C:40]([F:42])[C:39]([F:43])=[CH:38][C:37]=1[F:44]>CO>[O:31]=[C:32]([N:46]1[CH2:51][CH2:50][N:49]2[C:52]([C:55]([F:58])([F:57])[F:56])=[N:53][N:54]=[C:48]2[CH2:47]1)[CH2:33][C@@H:34]([NH2:45])[CH2:35][C:36]1[CH:41]=[C:40]([F:42])[C:39]([F:43])=[CH:38][C:37]=1[F:44]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 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 12362976dibenzoyl-L(+)tartaric acid

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-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
62.5 °C

Procedure

In a 50 mL three neck flask IPA (5 mL) and Dibenzoyl-L-tartaric acid (1.75 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-94%) dissolved in methanol (6 mL) was added into reaction mixture at 60-65. It was stirred for 60 min. at 60-65° C. Solid salt was precipitated. It was gradually cooled to room temperature over a period of 2 to 3 hrs. The salt was filtered and washed with a mixture of IPA: MeOH (2:1, 10 mL). 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.-1.08 g, % Y-29%, Purity by HPLC-99.1%, % Chiral purity by HPLC of R-isomer 76.7%).

Workup

  1. additionwas added into reaction mixture at 60-65
  2. customSolid salt was precipitated
  3. temperatureIt was gradually cooled to room temperature over a period of 2 to 3 hrs
  4. filtrationThe salt was filtered
  5. washwashed with a mixture of IPA: MeOH (2:1, 10 mL)
  6. additionAn enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of mixture of (2R)

Sources & evidence

ORD record
ord-7dbecd479f5a4b97b90160264c973a6b
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Linked notes

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