Sodium Bicarbonate → 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 445979Notes

Reaction equation

HRID 445979 reaction equation
[O:1]=[C:2]([N:16]1[CH2:21][CH2:20][N:19]2[C:22]([C:25]([F:28])([F:27])[F:26])=[N:23][N:24]=[C:18]2[CH2:17]1)[CH2:3][CH:4]([NH2:15])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14].O.[C:30]([C@@:38]([C:53]([OH:55])=[O:54])([OH:52])[C@@:39]([C:44](=[O:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)([OH:43])[C:40]([OH:42])=[O:41])(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C([O-])(O)=O.[Na+].O=C(N1CCN2C(C(F)(F)F)=NN=C2C1)C[C@@H](N)CC1C=C(F)C(F)=CC=1F>CC(O)C.CO.C(OCC)(=O)C>[C:44]([C@@:39]([C:40]([OH:42])=[O:41])([OH:43])[C@@:38]([C:30](=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([OH:52])[C:53]([OH:55])=[O:54])(=[O:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.[O:1]=[C:2]([N:16]1[CH2:21][CH2:20][N:19]2[C:22]([C:25]([F:28])([F:27])[F:26])=[N:23][N:24]=[C:18]2[CH2:17]1)[CH2:3][CH:4]([NH2:15])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 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-one2×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-oneHCID 130366077Dibezoyl-L-tartaric acid monohydrate

Product 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 12362976dibenzoyl-L(+)tartaric acid

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21255859Isopropanol methanolSolvent

Procedure

Dibenzoyl-L-tartaric acid salt of 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 prepared by reacting 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 with Dibezoyl-L-tartaric acid monohydrate (1.18 molar equivalent) in IPA-methanol at 25-70° C. till solid mass precipitated out. The salt was filtered and washed with IPA; an enantiomerically enriched desired isomer was obtained. The salt was taken into ethyl acetate. It was basified with aq. NaHCO3. Ethyl acetate layer was separated and washed with water and brine solution. Ethyl acetate extract was collected and dried over anhydrous sodium sulfate. Ethyl acetate was distilled out to obtain a 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 (% Purity by HPLC-98%, % Chiral purity by HPLC of R-isomer 70%).

Workup

  1. customat 25-70° C.
  2. customprecipitated out
  3. filtrationThe salt was filtered
  4. washwashed with IPA
  5. customwas obtained
  6. customEthyl acetate layer was separated
  7. washwashed with water and brine solution
  8. extractionEthyl acetate extract
  9. customwas collected
  10. dry with materialdried over anhydrous sodium sulfate
  11. distillationEthyl acetate was distilled out
  12. customto obtain

Sources & evidence

ORD record
ord-30843d86d5824eff97e1c99e55e8a66d
Source dataset
uspto-grants-2013_07
Patent number
US08476437B2

Reaction notes

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