ACCEPTED MANUSCRIPT
methylbenzyl)-2,3,4,9-tetrahydro-1H-carbazol-2-amine
which
was
converted
to
corresponding hydrochloride 13o (0108g, 36.8%) by using IPA-HCl and ethyl acetate as
solvent.
Yield: 36.8%; Off-white solid; mp: 210-212 °C; 1H-NMR (300MHz, DMSO-d6):
δ 1.91-1.92
(m, 1H), 2.32-2.33(m, 2H), 2.34 (s, 3H), 2.50-2.60 (m, 1H), 2.77-2.83 (m, 1H), 2.95-2.99 (m,
1H), 3.20-3.33 (m, 1H), 3.53 (s, 1H), 4.23 (s, 2H), 6.84 (d, J = 8.1 Hz, 1H), 7.15 (d, J = 8.1
Hz, 2H), 7.26 (d, J = 7.2 Hz, 2H), 7.49 (d, J = 7.2 Hz, 2H), 7.26-7.38 (bs, 2H), 10.62 (s, 1H);
13C-NMR(100 MHz, DMSO-d6): δ 19.18, 21.28, 21.70, 25.98, 26.46, 47.72, 54.16, 107.46,
111.00, 117.69, 122.60, 127.14, 129.64(3C), 130.59(3C), 131.1, 135.02, 138.75; MS (ESI)
m/z: 305.1[M+H]+; HPLC Retention time: 3.551 min., Purity: 93.05%(Method A).
4.1.35. 9-Methyl-1,3,4,9-tetrahydrospiro[carbazole-2,2'-[1,3]dioxolane] (14)
Sodium hydride (0.698 g, 17.45 mmol) was added to a stirred solution of 1,3,4,9-
tetrahydrospiro[carbazole-2,2'-[1,3]dioxolane] 9 (2.0 g, 8.72 mmol) in THF (50 mL) at 0-
5°C. Stirred reaction mixture for 10 min. and added slowly iodomethane (1.636 mL, 26.2
mmol). After being stirred at same temperature for 1 h stirred reaction mixture overnight at
25 – 30 °C. Quenched an excess of sodium hydride with methanol, evaporated solvent on
rotavapor to thick residue which was diluted with water (50 mL), extracted with ethyl acetate
(2 x 50mL). Combined organic layers were washed brine (50 mL), dried over anhydrous
sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to get
crude product which was purified by silica gel (60/120) column chromatography in Pet.
Ether: Ethyl acetate; 1:1 as elute to get title compound 14 (1.7g, 80.0%).
Yield: 80.0%; Viscous Oil; 1H-NMR (300MHz, CDCl3):
δ 2.05 (t, J = 6.3 Hz, 2H), 2.91 (t, J
= 6.3 Hz, 2H), 3.00 (s, 2H), 3.62 (s, 3H), 4.09 (s, 4H), 7.08 (t, J = 6.9 Hz, 1H), 7.17 (t, J = 6.6
Hz, 1H), 7.26(d, J = 9.3 Hz, 1H), 7.49(d, J = 7.8 Hz, 1H); MS (ESI) m/z: 252.1[M+H]+.
4.1.36. 9-Methyl-1,3,4,9-tetrahydro-2H-carbazol-2-one (15)
To a stirred suspension of 9-methyl-1,3,4,9-tetrahydrospiro[carbazole-2,2'-[1,3]dioxolane] 14
(1.6g, 6.58 mmol) in methanol (30 mL) charged slowly 10% aqueous sulphuric acid (20 mL)
at 25 - 30°C and stirred resulting reaction mixture at same temperature for 30 h. Diluted
reaction mixture with water(150 mL) and extracted with ethyl acetate(2 x 100mL). Combined
organic layers were washed with water (100 mL) and brine (100 mL). The organic layer was
dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under
reduced pressure to get crude product which was purified silica gel (60/120) column