Trifluoroacetic acid → N-[4-[(3S)-3-aminopiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl]-6-(2,6-difluoro-4-methylsulfonylphenyl)-5-fluoropyridine-2-carboxamide

HRID 1499564노트

반응식

HRID 1499564 반응식
C([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH:28][C:29]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[C:33]([C:38]4[C:43]([F:44])=[CH:42][C:41]([S:45]([CH3:48])(=[O:47])=[O:46])=[CH:40][C:39]=4[F:49])[N:32]=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.[OH-].[Na+].C(O)(C(F)(F)F)=O>CO.C1COCC1.C(Cl)Cl>[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[CH:36]=[CH:35][C:34]([F:37])=[C:33]([C:38]4[C:39]([F:49])=[CH:40][C:41]([S:45]([CH3:48])(=[O:46])=[O:47])=[CH:42][C:43]=4[F:44])[N:32]=3)=[O:30])=[CH:11][N:10]=[C:9]3[CH:5]([OH:4])[CH2:6][CH2:7][C:8]=23)[CH2:15]1

참가 물질

7

반응물 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 867267864-{(3S)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-[({6-[2,6-difluoro-4-(methylsulfonyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

생성물 1

HCID 86726787N-[4-[(3S)-3-aminopiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl]-6-(2,6-difluoro-4-methylsulfonylphenyl)-5-fluoropyridine-2-carboxamide

시약·촉매·용매 3

HCID 887Methanol용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

4-{(3S)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-[({6-[2,6-difluoro-4-(methylsulfonyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate (11.0 mg, 0.0156 mmol) was dissolved in MeOH (0.04 mL) and THF (0.20 mL), then 1.0 M aq. NaOH (0.062 mL, 0.062 mmol) was added. The reaction mixture was stirred at room temperature for 30 min. The organic solvents and trace of water were removed under vacuum to give a crude intermediate. The intermediate was dissolved in DCM (0.16 mL) and TFA (0.16 mL, 2.1 mmol) was then added. The reaction mixture was stirred at room temperature for 30 min. The solution was concentrated under reduced pressure and the residue was diluted with MeOH, filtered and purified by preparative LC-MS (XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH) to give both diastereoisomers of the title compound as white powders. On analytical HPLC (Waters SunFire™ C18, 2.1×50 mm, 5 μm; flow rate 3 mL/min.; injection volume 2 μL; gradient from 2 to 80% B in 3 minutes (A=water with 0.025% TFA, B=MeCN)), the diastereoisomers had the following properties:

후처리

  1. customThe organic solvents and trace of water were removed under vacuum
  2. customto give a crude intermediate
  3. stirringThe reaction mixture was stirred at room temperature for 30 min
  4. concentrationThe solution was concentrated under reduced pressure
  5. additionthe residue was diluted with MeOH
  6. filtrationfiltered
  7. custompurified by preparative LC-MS (XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min.
  8. washeluting with a gradient of MeCN and water with 0.1% NH4OH)

출처 및 근거

ORD 기록
ord-0f94278e0d304d50ae549a77ede81d56
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09200004B2

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