Sodium Carbonate → 7-(3-Phenyl-indole-1-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline Hydrochloride

3-Phenylindole [Heterocycl. Commun. (2000), 6(1), 59-62](2 mmol, 390 mg), was added to a stirred suspension of sodium hydride (40% oil dispersion, 88 mg, 2.2 mmol) in tetrahydrofuran (15 ml). When the effervescence ceased, 7-chlorosulfonyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid 2,2,2-trichloro-ethyl ester (D7) (840 mg, 2 mmol) was added and the mixture stirred at RT for 36 hours. The mixture was treated with saturated aq sodium carbonate (100 ml) and extracted with dichloromethane (3×50 ml). The combined extracts were dried (MgSO4) filtered and evaporated to afford a brown oil which was dissolved in THF (20 ml) and treated with sodium dihydrogen phosphate (10 ml) and zinc dust (1.0 g). The mixture was stirred vigorously for 36 h, filtered, washing the solid with water (10 ml) and THF (10 ml). The filtrate was treated with 10% aqueous potassium carbonate (20 ml) and the mixture extracted with dichloromethane (3×50 ml). The combined organic phase was dried (MgSO4), filtered, evaporated and the residue purified by flash chromatography (methanol-dichloromethane-aqueous ammonia) to afford the free base of the title compound δH (CHCl3)/ppm 2.73-2.79 (2H, m), 3.06 (2H, app.t), 3.94, 3.97 (2H, 2s), 7.03-7.69 (11H, m), 7.78 (1H, d), 8.04 (1H, d), MS[ES]: m/z (MH+) 389. This was converted to the title compound (E35) by treatment with 1M HCl in diethyl ether. Rf silica gel (1% (35% aq. NH3), 9% MeOH, 90% CHCl3) 0.40; δmax (CHCl3) 3422, 2959, 2761, 1604, 1445, 1372, 1166, 1134 cm-1; δH (CHCl3) 1.7 (2H, br.s), 3.09-3.10 (2H, m), 3.28-3.30 (2H, m), 4.24, 4.29 (2H, 2s), 7.19-7.78 (12H, m), 8.04 (1H, d); m.p. (diethyl ether-methanol) (with decomposition) 193-197° C.

1. extractionextracted with dichloromethane (3×50 ml)
2. dry with materialThe combined extracts were dried (MgSO4)
3. filtrationfiltered
4. customevaporated
5. customto afford a brown oil which
6. stirringThe mixture was stirred vigorously for 36 h
7. filtrationfiltered
8. washwashing the solid with water (10 ml) and THF (10 ml)
9. additionThe filtrate was treated with 10% aqueous potassium carbonate (20 ml)
10. extractionthe mixture extracted with dichloromethane (3×50 ml)
11. dry with materialThe combined organic phase was dried (MgSO4)
12. filtrationfiltered
13. customevaporated
14. customthe residue purified by flash chromatography (methanol-dichloromethane-aqueous ammonia)

ORDレコード

ord-0a864816d0694dd2bc578d18dbbc315f

出典データセット

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06849644B2