Formic Acid → (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 445975Notes

Reaction equation

HRID 445975 reaction equation
CC(O)C.O.C([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.[O:32]=[C:33]([N:47]1[CH2:52][CH2:51][N:50]2[C:53]([C:56]([F:59])([F:58])[F:57])=[N:54][N:55]=[C:49]2[CH2:48]1)[CH2:34][CH:35]([NH2:46])[CH2:36][C:37]1[CH:42]=[C:41]([F:43])[C:40]([F:44])=[CH:39][C:38]=1[F:45].C(O)=O>CO>[O:32]=[C:33]([N:47]1[CH2:52][CH2:51][N:50]2[C:53]([C:56]([F:59])([F:58])[F:57])=[N:54][N:55]=[C:49]2[CH2:48]1)[CH2:34][C@@H:35]([NH2:46])[CH2:36][C:37]1[CH:42]=[C:41]([F:43])[C:40]([F:44])=[CH:39][C:38]=1[F:45]

Participants

6

Reactant 4

HCID 284Formic AcidHCID 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 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-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 monohydrate (0.925 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 methanol (6 mL) and formic acid (0.112 g) 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 2-3 h. The salt was filtered and washed with a mixture of IPA: MeOH (2:1). 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.-1.32 g, % Y-34.6%, Purity by HPLC-99.6%, % Chiral purity by HPLC of R-isomer 75.7%).

Workup

  1. customSolid salt was precipitated
  2. temperatureIt was gradually cooled to room temperature over a period of 2-3 h
  3. filtrationThe salt was filtered
  4. washwashed with a mixture of IPA: MeOH (2:1)
  5. additionAn enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of mixture of (2R)

Sources & evidence

ORD record
ord-e5839ccfde2140fa83fbe73ef5e1b702
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Reaction notes

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