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Synlett 2008(10): 1479-1482  
DOI: 10.1055/s-2008-1078426
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of New Cyclopropanated Tryptamine Analogues

Claude Szalataa, Janos Sapia, Jan Szymoniakb, Philippe Bertus*b,c, Stéphane Gérard*a
a Institut de Chimie Moléculaire de Reims, UMR CNRS 6229, Faculté de Pharmacie, Université de Reims-Champagne-Ardenne, 51 rue Cognacq-Jay, 51096 Reims Cedex, France
e-Mail: stephane.gerard@univ-reims.fr;
b Institut de Chimie Moléculaire de Reims, , UMR CNRS 6229, UFR Sciences, Université de Reims-Champagne-Ardenne, BP 1039, 51687 Reims Cedex 2, France
c CNRS and Université du Maine, UMR 6011, UCO2M, 72085 Le Mans Cedex 9, France
Fax: +33(2)43833902; e-Mail: philippe.bertus@univ-lemans.fr;
Further Information

Publication History

Received 17 March 2008
Publication Date:
16 May 2008 (online)

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Abstract

A series of tryptamine analogues bearing a cyclopropyl­amine unit was prepared, starting from 3-indolyl acetonitriles, through a MeTi(Oi-Pr)3-mediated cyclopropanation.

Key words

cyclopropanes - indoles - titanium - transition metals - tryptamines

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The ketone by-product might also be obtained by the hydrolysis of metallacycle B (Scheme [2] ). This assumption was ruled out by deuterolysis of the reaction media (no trace of deuterium was observed on the methyl moiety).

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General Procedure for the MeTi(O i -Pr) 3 -Mediated Cyclopropanation of Nitriles 10a-c and 11a,b (Table 1): To a solution of the nitrile (1 mmol) and MeTi(Oi-Pr)3 (1.5 mmol) in THF (10 mL) was added dropwise under argon the Grignard reagent (1.5 mmol). The yellow solution darkened gradually within 5 min. After stirring for 1.5 h, BF3·OEt2 was added (2 mmol). After 30 min, the dark mixture was quenched with 1 M HCl (10 mL). EtOAc (20 mL) was added, followed by 3 M NaOH (10 mL). The mixture was stirred until the blue aqueous solution become white. The aqueous phase was extracted with EtOAc (2 × 20 mL). After drying (MgSO4) and evaporation of the solvents, the crude material was purified by flash chromatography (EtOAc).

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Selected data: 1-[(1-Benzenesulfonyl-1 H -indol-3-yl)methyl]cyclopropylamine (12a): pale yellow solid; mp 97-98 °C. IR (neat): 3385, 1447, 1361, 1175 cm-1. 1H NMR (250 MHz, CDCl3): δ = 0.46-0.63 (m, 4 H), 1.50 (br s, 2 H, NH2), 2.72 (s, 2 H), 7.13-7.47 (m, 7 H), 7.78 (d, J = 7.7 Hz, 2 H), 7.94 (d, J = 8.3 Hz, 1 H). 13C NMR (63 MHz, CDCl3): δ = 14.5, 33.7, 35.7, 113.7, 119.8, 120.8, 123.2, 123.7, 124.7, 126.5, 129.1, 131.3, 133.7, 135.2, 137.9. HRMS (ES): m/z [M + H]+ calcd for C18H19N2O2S 327.1167; found: 327.1169.

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The cyclopropanation of unprotected 8 gave only a low yield of the primary cyclopropylamine.

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Selected data: N , N -Dimethyl-1-[(1-benzenesulfonyl-1 H -indol-3-yl)methyl]cyclopropylamine (6a): yellow oil. IR (neat): 3365, 2916, 2845, 1634, 1445, 1264, 1119 cm-1. 1H NMR (300 MHz, CDCl3): d = 0.25-0.57 (m, 4 H), 2.45 (s, 6 H), 3.01 (s, 2 H), 7.25-7.52 (m, 7 H), 7.80-7.83 (m, 2 H), 7.98 (d, J = 8.1 Hz, 1 H). 13C NMR (75 MHz, CDCl3): d = 13.3, 21.1, 40.9, 43.7, 113.9, 119.6, 120.3, 123.3, 124.2, 124.7, 126.5, 129.1, 131.7, 133.7, 135.1, 138.0. HRMS (EI): m/z [M+·] calcd for C20H22N2O2S: 354.1402; found: 354.1398. N , N -Dimethyl-1-[(1-methyl-2-vinyl-1 H -indol-3-yl)methyl]cyclopropylamine (7a): yellow oil. IR (neat): 3054, 2986, 2845, 1628, 1437, 1262 cm-1. 1H NMR (300 MHz, CDCl3): d = 0.30-0.55 (m, 4 H), 2.63 (s, 6 H), 3.30 (s, 2 H), 3.70 (s, 3 H), 5.50 (dd, J = 1.2, 11.9 Hz, 1 H), 5.69 (dd, J = 1.2, 17.9 Hz, 1 H), 7.07 (dd, J = 11.9, 17.9 Hz, 1 H), 7.02-7.38 (m, 3 H), 7.54 (d, J = 7.4 Hz, 1 H). 13C NMR (75 MHz, CDCl3): d = 12.2, 18.6, 30.7, 40.4, 44.7, 109.1, 117.3, 118.9, 119.3, 122.1, 125.9, 128.6, 128.7, 135.2, 137.2. HRMS (ES): m/z [M + H+] calcd for C17H23N2: 255.1861; found: 255.1855.