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

反応式

HRID 445967 の反応式
[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]

参加物

8

反応物 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 回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

生成物 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

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 21255859Isopropanol methanol溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-8a21793e304f4c3eba9538e618a0eba4
出典データセット
uspto-grants-2013_07
特許番号
US08476437B2

関連ノート

読み込み中…