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

HRID 1766266Notes

Reaction equation

HRID 1766266 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Sources & evidence

ORD record
ord-b637774bfa06412fa064a5aa60da6eaf
Source dataset
uspto-grants-2007_06
Patent number
US07230011B2

Reaction notes

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