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

HRID 1766266노트

반응식

HRID 1766266 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

출처 및 근거

ORD 기록
ord-b637774bfa06412fa064a5aa60da6eaf
출처 데이터셋
uspto-grants-2007_06
특허 번호
US07230011B2

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