Compound 8

8-(((3-(3-(hex-5-yn-1-yl)-3H-diazirin-3-yl)propyl)thio)methyl)-N-(4-methylbenzyl)-4H-thieno[3,2-c]thiochromene-2-carboxamide-5-dioxide

From: A small molecule interacts with VDAC2 to block mouse BAK-driven apoptosis

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Compound data: NMR

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

To a mixture of carboxylic acid (32) (15 mg, 0.031 mmol) in DCM (1 mL) was added EDCI.HCl (18 mg, 0.092 mmol) followed by benzylamine (10 μL, 0.077 mmol) and DMAP (4 mg, 0.031 mmol). The mixture was stirred for 0.5 h and HPLC analysis showed 50% conversion. After 1 h the reaction was complete and the mixture was concentrated onto silica and purified by chromatography using ethyl acetate/cyclohexane (20:50). Concentration of the appropriate fractions (Rf = 0.5, 50% EtOAc/c-Hex) afforded the desired compound 8 (5.4 mg, 30%) as a white solid. 1H-NMR (600 MHz; CDCl3): δ 1.17-1.24 (m, 2H), 1.31-1.40 (m, 4H), 1.51-1.45 (m, 4H), 1.92 (t, J = 2.6 Hz, 1H), 2.11 (td, J = 6.9, 2.6 Hz, 2H), 2.39-2.35 (m, 5H), 3.74 (s, 2H), 4.40 (s, 2H), 4.57 (d, J = 5.6 Hz, 2H), 6.19 (t, J = 5.5 Hz, 1H), 7.16 (d, J = 7.9 Hz, 2H), 7.23, (d, J = 7.9 Hz, 2H), 7.35 (s, 1H), 7.45 (dd, J = 8.0, 1.6, 1H), 7.57 (d, J = 1.3 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H). 13C-NMR (75 MHz, CDCl3): δ 18.2, 21.1, 22.9, 23.3, 27.8, 28.2, 30.9, 31.7, 32.4, 35.8, 44.1, 51.3, 68.6, 83.9, 124.6, 125.9, 128.0 (2), 128.7, 128.8, 129.5 (2), 129.6, 130.4, 132.3, 134.4, 137.2, 137.7, 139.0, 145.5, 160.4. LCMS (ES+), m/z = 592.00 [M+H]+. HRMS (+ESI), m/z = 592.1765[M+H]+ (calculated:592.1757).