(R)-1-amino-2,3-dihydro-1H-indene-4-carbonitrile hydrochloride

Synthesis

General procedure for the synthesis of (R)-1-amino-2,3-dihydro-1H-indene-4-carbonitrile hydrochloride from the compound (CAS: 1306763-28-9): crude oil (i)-N-((R)-4-cyano-2,3-dihydro-7H-inden-1-yl)-2-methylpropane-2-sulfinamide (INT-5, 52.9 g, 0.20 mol ) was dissolved in methanol (200 mL) and a dioxane solution of 4N HCl (152.0 mL, 0.60 mol) was added. The resulting yellow suspension was stirred at room temperature for 1.5 hours. The crude reaction mixture was diluted with methanol (500 mL) and filtered to remove some of the Ti by-products. The filtrate was concentrated and the solid obtained was refluxed in acetonitrile (500 mL). The resulting white solid was collected to give 13.0 g (31% overall yield in three steps) of (R)-1-amino-2,3-dihydro-1H-indene-4-carbonitrile hydrochloride (6).LCMS-ESI (m/z) Calculated (C10H11N2): 158.2; Measured: 142.0 [M-NH2]+, tR = 0.84 min.1H NMR (400 MHz, DMSO): 158.2; Measured: 142.0 [M-NH2]+, tR = 0.84 min. MHz, DMSO) δ 8.61 (s, 3H), 7.96 (d, J = 7.7 Hz, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.52 (t, J = 7.7 Hz, 1H), 4.80 (s, 1H), 3.23 (ddd, J = 16.6, 8.7, 5.2 Hz, 1H), 3.05 (ddd, J = 16.6, 8.6, 6.3 Hz, 1H), 2.62-2.51 (m, 1H), 2.15-2.01 (m, 1H).13C NMR (101 MHz, DMSO) δ 148.09, 141.15, 132.48, 130.32, 127.89, 117.27, 108.05, 54.36. 39.08, 29.64.

References

[1] Patent: WO2011/60389, 2011, A1. Location in patent: Page/Page column 91-92
[2] Patent: WO2015/66515, 2015, A1. Location in patent: Page/Page column 77-78
[3] Patent: WO2018/64356, 2018, A1. Location in patent: Page/Page column 56