Methanol → N-{4-[(3S)-3-Aminopiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide

HRID 1499453ノート

反応式

HRID 1499453 の反応式
C([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH:28][C:29]([C:31]3[N:32]=[C:33]([C:36]4[C:41]([F:42])=[CH:40][CH:39]=[CH:38][C:37]=4[F:43])[S:34][CH:35]=3)=[O:30])[C:13]([N:14]3[CH2:19][CH2:18][CH2:17][C@H:16]([NH:20]C(OC(C)(C)C)=O)[CH2:15]3)=[C:8]2[CH2:7][CH2:6]1)(=O)C.CO.[OH-].[Na+].C(O)(C(F)(F)F)=O>C(Cl)Cl.C1COCC1>[NH2:20][C@H:16]1[CH2:17][CH2:18][CH2:19][N:14]([C:13]2[C:12]([NH:28][C:29]([C:31]3[N:32]=[C:33]([C:36]4[C:37]([F:43])=[CH:38][CH:39]=[CH:40][C:41]=4[F:42])[S:34][CH:35]=3)=[O:30])=[CH:11][N:10]=[C:9]3[CH:5]([OH:4])[CH2:6][CH2:7][C:8]=23)[CH2:15]1

参加物

7

反応物 4

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 867266964-{(3S)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-({[2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

生成物 1

HCID 86726697N-{4-[(3S)-3-Aminopiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

4-{(3S)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-({[2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate (4.0 mg, 0.0065 mmol) was mixed with MeOH (77 μL), THF (39 μL) and 1.0 M NaOH (42 μL, 0.042 mmol). The reaction mixture was stirred at room temperature for 30 min. The organic solvents were removed under reduced pressure. The resulting aqueous solution was diluted with aq. NH4Cl and extracted twice with EtOAc. The combined organic layers were dried, filtered and concentrated to give an intermediate. The intermediate was dissolved in a mixture of DCM (0.066 mL) and TFA (0.066 mL, 0.86 mmol). The resulting solution was stirred at room temperature for 30 min., then concentrated under reduced pressure. The residue was diluted with MeOH, neutralized with NH4OH, filtered and purified by preparative LC-MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min., eluting with a gradient of MeCN and water with 0.15% NH4OH) to give two diastereoisomers of the title compound as white powders.

後処理

  1. customThe organic solvents were removed under reduced pressure
  2. additionThe resulting aqueous solution was diluted with aq. NH4Cl
  3. extractionextracted twice with EtOAc
  4. customThe combined organic layers were dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give an intermediate
  8. stirringThe resulting solution was stirred at room temperature for 30 min.
  9. concentrationconcentrated under reduced pressure
  10. additionThe residue was diluted with MeOH
  11. filtrationfiltered
  12. custompurified by preparative LC-MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min.
  13. washeluting with a gradient of MeCN and water with 0.15% NH4OH)

出典と根拠

ORDレコード
ord-a809d04742634cd9a5fe2c9f03831703
出典データセット
uspto-grants-2015_12
特許番号
US09200004B2

反応ノート

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