Methyl 3-mercaptopropionate → Tert-butyl 4-((2-(5-(3-methoxy-3-oxopropylthio)-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate

HRID 335262Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 335262
Br[C:2]1[CH:3]=[C:4]([O:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH2:14][CH:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[N:13]=2)=[N:6][CH:7]=1.C(N(C(C)C)C(C)C)C.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(CC)(CC)C=3C=CC=2)C=CC=CC=1.[SH:88][CH2:89][CH2:90][C:91]([O:93][CH3:94])=[O:92]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.O1CCOCC1>[CH3:94][O:93][C:91](=[O:92])[CH2:90][CH2:89][S:88][C:2]1[CH:3]=[C:4]([O:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH2:14][CH:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[N:13]=2)=[N:6][CH:7]=1

Komponenten

8

Edukt 4

HCID 18050Methyl 3-mercaptopropionateHCID 81531DiisopropylethylamineHCID 57742615Tert-butyl 4-((2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylateHCID 866782334,5-bis(diphenylphosphino)-9,9-diethyl-9H-xanthene

Produkt 1

HCID 57742831Tert-butyl 4-((2-(5-(3-methoxy-3-oxopropylthio)-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylateAusbeute 94,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

The atmosphere above a mixture of tert-butyl 4-((2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate (1.52 g, 2.79 mmol), N-ethyl-N-isopropylpropan-2-amine (0.971 mL, 5.57 mmol), 4,5-bis(diphenylphosphino)-9,9-diethyl-9H-xanthene (0.161 g, 0.279 mmol), and dioxane (25 mL) was purged with nitrogen. Methyl 3-mercaptopropanoate (0.332 mL, 3.07 mmol) and Pd2dba3 (0.128 g, 0.139 mmol) were added, and the reaction was heated at 95° C. overnight. The reaction was cooled to ambient temperature and filtered through celite. The filtrate was concentrated and purified by MPLC (Biotage) eluting with 3:2 hexane:ethyl acetate to afford the title compound (1.54 g, 94.5% yield) as a tacky white solid: 1H NMR (CDCl3) δ 8.70 (s, 1H), 8.16 (s, 1H), 7.40 (t, 2H), 7.24 (t, 1H), 7.14 (s, 1H), 7.06 (d, 2H), 6.46 (s, 1H), 4.08 (m, 2H), 3.65 (s, 3H), 2.99 (t, 2H), 2.67 (m, 2H), 2.56 (d, 2H), 2.55 (t, 2H), 1.85 (m, 1H), 1.66 (m, 2H), 1.45 (s, 9H), 1.16 (m, 2H).

Aufarbeitung

  1. customwas purged with nitrogen
  2. temperatureThe reaction was cooled to ambient temperature
  3. filtrationfiltered through celite
  4. concentrationThe filtrate was concentrated
  5. custompurified by MPLC (Biotage)
  6. washeluting with 3:2 hexane

Quellen und Nachweise

ORD-Eintrag
ord-f8da8bb3fe3c4f5ea05c331e8e912b26
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08883828B2

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