4-(Pyrrolidin-1-yl)butan-1-amine → 3-(2,5-Difluoro-4-methyl-benzyloxy)-5-[3-(4-pyrrolidin-1-yl butyl)-ureido]-isothiazole-4-carboxylic acid amide

HRID 750579

Reaktionsgleichung

Reaktionsgleichung von HRID 750579
C1(O[C:8](=[O:29])[NH:9][C:10]2[S:14][N:13]=[C:12]([O:15][CH2:16][C:17]3[CH:22]=[C:21]([F:23])[C:20]([CH3:24])=[CH:19][C:18]=3[F:25])[C:11]=2[C:26](=[O:28])[NH2:27])C=CC=CC=1.[N:30]1([CH2:35][CH2:36][CH2:37][CH2:38][NH2:39])[CH2:34][CH2:33][CH2:32][CH2:31]1>O1CCCC1>[F:25][C:18]1[CH:19]=[C:20]([CH3:24])[C:21]([F:23])=[CH:22][C:17]=1[CH2:16][O:15][C:12]1[C:11]([C:26]([NH2:27])=[O:28])=[C:10]([NH:9][C:8]([NH:39][CH2:38][CH2:37][CH2:36][CH2:35][N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[O:29])[S:14][N:13]=1

Komponenten

4

Edukt 2

HCID 27627624-(Pyrrolidin-1-yl)butan-1-amineHCID 54330906[4-Carbamoyl-3-(2,5-difluoro-4-methyl-benzyloxy)-isothiazol-5-yl]carbamic acid phenyl ester

Produkt 1

HCID 539988383-(2,5-Difluoro-4-methyl-benzyloxy)-5-[3-(4-pyrrolidin-1-yl butyl)-ureido]-isothiazole-4-carboxylic acid amideAusbeute 81,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
47.5 °C

Versuchsvorschrift

A mixture of [4-carbamoyl-3-(2,5-difluoro-4-methyl-benzyloxy)-isothiazol-5-yl]-carbamic acid phenyl ester (0.34 g, 0.81 mmol), 4-pyrrolidinobutylamine (0.12 g, 0.81 mmol) and tetrahydrofuran (2.8 mL) was shaken at 45-50° C. for 24 hours. The mixture was concentrated and purified by radial chromatography (4 mm plate, CH3OH—CHCl3—NH4OH (10:89:1) to (15:84:1)), affording 0.31 g of the title compound as a colorless solid. The material was dissolved in ca. 10 mL of 4:1 methanol-chloroform at −10° C. and was treated with a solution of methanesulfonic acid (0.043 mL in 0.5 mL of CH3OH). After stirring for 5 minutes, the mixture was concentrated in vacuo, and the residue was triturated with methanol-ether, affording 0.35 g of the title compound (82%) as a colorless solid. HPLC ret. time: 3.3 minutes. 1H NMR (400 MHz, D2O) δ 6.74 (dd, 1H, J=6.0, 9.6 Hz), 6.63 (dd, 1H, J=6.4, 10.4 Hz), 4.61 (s, 2H), 3.44 (m, 2H), 3.05-2.98 (m, 4H), 2.98-2.81 (m, 2H), 2.62 (s, 3H), 1.95-1.93 (m, 4H), 1.83-1.80 (m, 2H), 1.6-1.5 (m, 2H), 1.4-1.3 (m, 2H) ppm; MS (APCl, m/z): 468 [M+H]+.

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. custompurified by radial chromatography (4 mm plate, CH3OH—CHCl3—NH4OH (10:89:1) to (15:84:1))

Quellen und Nachweise

ORD-Eintrag
ord-2836c9c537a84a4c84ad47a196df1312
Quelldatensatz
uspto-grants-2008_07
Patentnummer
US07405218B2

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