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 445967

반응식

HRID 445967 반응식
[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]

참가 물질

8

반응물 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-one2회HCID 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

생성물 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

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 21255859Isopropanol methanol용매

실험 절차

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 (1.0 mole) 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%).

후처리

  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

출처 및 근거

ORD 기록
ord-8a21793e304f4c3eba9538e618a0eba4
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08476437B2

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