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Dichloromethane → N-{4-[(3R,4R,5S)-3-Amino-4-hydroxy-5-methylpiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide

HRID 1499497
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Reaktionsgleichung

Reaktionsgleichung von HRID 1499497
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]([C:15]([NH:17][C:18]2[C:19]([N:28]3[CH2:33][C@H:32]([CH3:34])[C@@H:31]([OH:35])[C@H:30]([NH:36]C(=O)OC(C)(C)C)[CH2:29]3)=[C:20]3[CH2:26][CH2:25][CH:24]([OH:27])[C:21]3=[N:22][CH:23]=2)=[O:16])[CH:12]=[CH:11][C:10]=1[F:44].C(O)(C(F)(F)F)=O.C(Cl)Cl>>[NH2:36][C@H:30]1[C@H:31]([OH:35])[C@@H:32]([CH3:34])[CH2:33][N:28]([C:19]2[C:18]([NH:17][C:15]([C:13]3[CH:12]=[CH:11][C:10]([F:44])=[C:9]([C:3]4[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=4[F:8])[N:14]=3)=[O:16])=[CH:23][N:22]=[C:21]3[CH:24]([OH:27])[CH2:25][CH2:26][C:20]=23)[CH2:29]1
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Komponenten

4

Edukt 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 86726726tert-Butyl {(3R,4R,5S)-1-[3-({[6-(2,6-difluorophenyl)-5-fluoropyridin-2-yl]carbonyl}amino)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl]-4-hydroxy-5-methylpiperidin-3-yl}carbamate

Produkt 1

HCID 86726727N-{4-[(3R,4R,5S)-3-Amino-4-hydroxy-5-methylpiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide

Versuchsvorschrift

A mixture of tert-butyl {(3R,4R,5S)-1-[3-({[6-(2,6-difluorophenyl)-5-fluoropyridin-2-yl]carbonyl}amino)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl]-4-hydroxy-5-methylpiperidin-3-yl}carbamate (6 mg, 0.01 mmol) and TFA in DCM (4.0 M; 2.0 mL, 8.0 mmol) was stirred at room temperature for 1 h. After removal of the solvent, the residue was then diluted with MeOH (4 mL) and NH4OH solution (0.5 mL) and filtered. The filtrate was purified by preparative LCMS (pH=10 method; XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.15% NH4OH) to give two diastereoisomers of the title compound as a white powders.

Aufarbeitung

  1. customAfter removal of the solvent
  2. additionthe residue was then diluted with MeOH (4 mL) and NH4OH solution (0.5 mL)
  3. filtrationfiltered
  4. customThe filtrate was purified by preparative LCMS (pH=10 method
  5. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.15% NH4OH)

Quellen und Nachweise

ORD-Eintrag
ord-81aa3babe3244f2e991341bb8fbc1964
Quelldatensatz
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09200004B2

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