2,6-Lutidine → 2,6-Difluorobenzenesulfonic acid 1-benzyl-3-(1-methylpiperidin-4-yl)-1H-indol-5-yl ester hydrochloride

HRID 1766266Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1766266
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([OH:17])=[CH:14][CH:15]=2)[C:10]([CH:18]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]2)=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=1[S:33]([Cl:36])(=[O:35])=[O:34].N1C(C)=CC=CC=1C>O1CCCC1>[ClH:36].[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][S:33]([C:27]3[C:28]([F:32])=[CH:29][CH:30]=[CH:31][C:26]=3[F:25])(=[O:35])=[O:34])=[CH:14][CH:15]=2)[C:10]([CH:18]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]2)=[CH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

5

Edukt 3

HCID 79372,6-LutidineHCID 27342712,6-Difluorobenzenesulfonyl chlorideHCID 179801081-Benzyl-3-(1-methylpiperidin-4-yl)-5-hydroxy-1H-indole

Produkt 1

HCID 865924762,6-Difluorobenzenesulfonic acid 1-benzyl-3-(1-methylpiperidin-4-yl)-1H-indol-5-yl ester hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

By a method similar to Example 48, using 1-benzyl-3-(1-methylpiperidin-4-yl)-5-hydroxy-1H-indole (320 mg, 1.0 mmol), 2,6-difluorobenzenesulfonyl chloride (234 mg, 1.1 mmol) in tetrahydrofuran (20 mL), 2,6-lutidine (255 μL, 2.2 mmol) provided 382 mg (77%) of the free base of the desired compound as a colorless oil. A portion of this oil (182 mg) was dissolved in methanol (10 mL) and treated with ammonium chloride (19.6 mg, 0.37 mmol, dissolved in 10 mL methanol). The resulting solution was placed in an ultrasound bath for 5 minutes before removing the solvent in vacuo. The resulting residue was triturated with diethyl ether. Filtration and drying of the precipitate afforded 160 mg (82%) of the title hydrochloride as a white solid: mp=225-227° C.; 1H NMR (400 MHz, dmso-d6): 7.93-7.82 (m, 1H), 7.46-7.30 (mm, 5H), 7.30-7.12 (m, 5H), 6.78 (dd, 1H, J=8.8, 2.0 Hz), 5.33 (s, 2H), 3.42-3.24 (m, 2H, overlapping with H2O), 3.04-2.84 (m, 3H), 2.68 (s, 3H), 2.00-1.78 (m, 4H); MS (ES+): m/e 496.9 (M+1); Calculated (for C27H26F2N2O3S.HCl): C 60.84, H 5.11, N 5.26; found: C 60.69, H 5.00, N 5.26.

Quellen und Nachweise

ORD-Eintrag
ord-b637774bfa06412fa064a5aa60da6eaf
Quelldatensatz
uspto-grants-2007_06
Patentnummer
US07230011B2

Notizen zur Reaktion

Wird geladen…