Water → 1-Cyclopropyl-3-(3-fluoro-4-(2-(5-((4-(2-fluoroethyl)piperazin-1-yl)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea

HRID 1400934Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1400934
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH2:30][N:31]6[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]6)=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:37])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].CS(O[CH2:49][CH2:50][F:51])(=O)=O.O>CN(C=O)C>[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH2:30][N:31]6[CH2:32][CH2:33][N:34]([CH2:49][CH2:50][F:51])[CH2:35][CH2:36]6)=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:37])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 680342-Fluoroethyl methanesulfonateHCID 674423881-Cyclopropyl-3-(3-fluoro-4-(2-(5-(piperazin-1-ylmethyl)pyridin-2-yl)thieno[3,2-b]-pyridin-7-yloxy)phenyl)urea

Produkt 1

HCID 866586031-Cyclopropyl-3-(3-fluoro-4-(2-(5-((4-(2-fluoroethyl)piperazin-1-yl)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 49 (70 mg, 0.111 mmol, scheme 26) in DMF (2 mL) were added K2CO3 (77 mg, 0.555 mmol) and 419 (79 mg, 0.555 mmol). The mixture was heated to 80° C. for 16 hours. Water was added to form a precipitate that was collected by filtration, rinsed with water and purified via Biotage [linear gradient 0-20%, (methanol/dichloromethane; SiliaFlash 10 g cartridge]. Title compound 420 was obtained as a white solid (38.9 mg, 62% yield). 1H NMR (500 MHz, DMSO-d6) δ (ppm): 8.68 (s, 1H), 8.53 (d, J=1.7 Hz, 1H), 8.51 (d, J=5.4 Hz, 1H), 8.31 (s, 1H), 8.23 (d, J=8.2 Hz, 1H), 7.85 (dd, J=8.1, 2.0 Hz, 1H), 7.72 (dd, J=13.5, 2.4 Hz, 1H), 7.37 (t, J=9.0 Hz, 1H), 7.22-7.17 (m, 1H), 6.64 (d, J=5.4 Hz, 1H), 6.54 (bd, J=2.3 Hz, 1H), 4.55 (t, J=4.9 Hz, 1H), 4.45 (t, J=4.9 Hz, 1H), 3.54 (s, 2H), 2.89-2.83 (m, 2H), 2.62 (t, J=5.0 Hz, 1H), 2.59-2.51 (m, 1H), 2.56 (t, J=5.1 Hz, 1H), 2.50-2.32 (m, 8H), 0.68-0.62 (m, 2H), 0.45-0.40 (m, 2H). MS (m/z): 565.23 (M+H).

Aufarbeitung

  1. customto form a precipitate that
  2. filtrationwas collected by filtration
  3. washrinsed with water
  4. custompurified via Biotage [linear gradient 0-20%

Quellen und Nachweise

ORD-Eintrag
ord-0ffdac3f7f5c4a8f9329551fee6d78b0
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08906852B2

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