Compound (R)-1

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InChIKey PZWNVUVKXINZKH-MRXNPFEDSA-N

Compound data: NMR

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

General Procedure: coupling procedure for the synthesis of chiral fragment probes: 3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanoic acid (0.1 mmol, 1 equiv.) and the commercially-available chiral amine (0.11 mmol, 1.1 equiv.) were dissolved in anhydrous dichloromethane (1.5 mL) in a 4 mL vial. DIPEA (2.2 equiv.), EDCI (1.1 equiv.) and HOAt (1.1 equiv.) were added. The reaction mixture was stirred overnight at room temperature or when TLC indicated reaction completed. The crude mixture was concentrated by blowing a constant stream of nitrogen over it to remove the excess solvent. The resulting mixture was diluted with ethyl acetate (5 mL) and washed with saturated aqueous NH₄Cl (5 mL), saturated aqueous NaHCO₃ (5 mL) and brine (5 mL). The organic phase was dried over anhydrous Na₂SO₄, concentrated by removing solvent under reduced pressure and purified by flash chromatography or preparative TLC. The chromatography was run with the indicated solvent and the product was eluted from the silica. Evaporation of the solvent resulted in the desired product. The title compound was synthesised following the General Procedure outlined above. The flash chromatography was run with n-hexane/ethyl acetate 3:1. 21.4 mg (72%) of the product were obtained. ¹H NMR (500 MHz, Chloroform-d) (70:30 mixture of rotamers, peaks corresponding to minor rotamer starred) δ 7.35 (m, 1.35H), 7.27 (m, 1.35H), 7.21 – 7.16* (m, 0.3H), 7.16 – 7.10 (m, 2H), 5.19* (dd, J = 8.1, 2.7 Hz, 0.3H), 4.88 (dd, J = 8.0, 2.4 Hz, 0.7H), 3.79 – 3.64 (m, 1.7H), 3.54* (ddd, J = 9.9, 8.6, 7.2 Hz, 0.3H), 2.45 – 2.32 (m, 0.7H), 2.29 – 2.18* (m, 0.3H), 2.09 (t, J = 7.6 Hz, 0.6H), 2.04 – 1.95 (m, 1.4H), 1.95 – 1.82 (m, 5.7H), 1.80 – 1.62 (m, 2.3H), 1.62 – 1.55 (m, 0.7H), 1.55 – 1.41 (m, 1.3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.10, 169.95, 143.53, 143.34, 129.28, 128.77, 127.82, 127.09, 125.80, 125.77, 83.22, 83.16, 77.69, 77.43, 77.18, 69.46, 61.99, 60.97, 47.92, 47.58, 36.76, 34.35, 33.03, 32.78, 28.85, 28.79, 28.23, 27.88, 24.07, 22.16, 13.73, 13.61. HRMS (m/z) calculated for C₁₈H₂₂N₃O [M+H]⁺: 296.1757; found: 296.1760.