Water → (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 445970Notes

Reaction equation

HRID 445970 reaction equation
O.O.C([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.[O:29]=[C:30]([N:44]1[CH2:49][CH2:48][N:47]2[C:50]([C:53]([F:56])([F:55])[F:54])=[N:51][N:52]=[C:46]2[CH2:45]1)[CH2:31][CH:32]([NH2:43])[CH2:33][C:34]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:35]=1[F:42]>CC(O)C>[O:29]=[C:30]([N:44]1[CH2:49][CH2:48][N:47]2[C:50]([C:53]([F:56])([F:55])[F:54])=[N:51][N:52]=[C:46]2[CH2:45]1)[CH2:31][C@@H:32]([NH2:43])[CH2:33][C:34]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:35]=1[F:42]

Participants

5

Reactant 3

HCID 962WaterHCID 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 3776IsopropanolSolvent2×

Conditions

Temperature
42.5 °C

Procedure

In a 50 mL three neck flask IPA (5 mL), water (2 mL) and Dibenzoyl-L-tartaric acid monohydrate (1.84 g) were taken. It was heated to 40-45° 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 IPA (5 mL) was added into reaction mixture at 60-65° C. It was stirred for 1 h at 60-65° C. It was gradually cooled to room temperature. Then it was further cooled to 0-5° C. and stirred for 1 h. The salt was filtered and washed with cold IPA. 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.-1.1 g, % Y-28.7%, Purity by HPLC-99.1%, % Chiral purity by HPLC of R-isomer 74%).

Workup

  1. additionwas added into reaction mixture at 60-65° C
  2. temperatureIt was gradually cooled to room temperature
  3. temperatureThen it was further cooled to 0-5° C.
  4. stirringstirred for 1 h
  5. filtrationThe salt was filtered
  6. washwashed with cold IPA
  7. additionAn enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of mixture of (2R)

Sources & evidence

ORD record
ord-0dd8f7ae26f24958926e8d16c9265654
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Reaction notes

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