Topic automatically created for discussing the designs at:
https://covid.postera.ai/covid/submissions/ab37bd51-7475-442e-bebd-10f4bc26f99e
Precursors available from UK suppliers
http://www.fluorochem.co.uk/Products/Product?code=062980
https://www.sigmaaldrich.com/catalog/product/aldrich/cds020852
Synthesis of a similar compound:
(E)-4-(dimethylamino)but-2-enoic acid hydrochloride (133.4 mg, 0.805 mmol, 1.5 equ) was dissolved in THF (5 ml) then was added trimethylamine (217.3 mg, 2.15 mmol, 4 equ) and T3P (683 mg, 1.07 mmol, 2 equ) (50% in Ethyl acetate (0.6400 ml)) was added. After 15 min aniline (50 mg, 0.54 mmol, 1 equ) was added and the reaction stirred overnight. Then 10 ml saturated sodium hydrogen carbonate solution was added and the solution extracted 3× with 10 ml DCM. The combined organic layers were dried over MgSO4, passed through a phase separator and evaporated to dryness. The residue was purified by flash chromatography eluting with a gradient of 0–9% methanol in DCM to give a mixture containing (E)-4-(dimethylamino)- N -phenyl-but-2-enamide (46 mg) as a pale yellow powder. This was purified by HPLC eluting with 5–95% acetonitrile in water (0.1% NH4) to give (E)-4-(dimethylamino)- N -phenyl-but-2-enamide (41 mg, 37%) as a white powder.
1H (400 MHz, CDCl3): δ 7.92 (1H, brs, H5), 7.57 (2H, d, J = 7.7 Hz, H3), 7.28 (2H, t, J = 7.9 Hz, H2), 7.08 (1H, t, J = 7.3 Hz, H1), 6.94 (1H, dt, J = 15.3, 6.1 Hz, H8), 6.14 (1H, dt, J = 15.3, 1.6 Hz, H7), 3.04 (2H, dd, J = 6.1, 1.5 Hz, H9), 2.23 (6H, s, H 10);
13C (100 MHz, CDCl3): δ 142.83 (C8), 129.20 ( C 2), 125.76 (C7), 124.56 (C1), 119.95 (C3), 60.53 (C9), 45.71 (C10)
HRMS m / z (ESI+) calcd for C12H17N2O [M+H]+: 205.1335, found 205.1350 (4.6 ppm)
Thanks for the reference! Our algorithms start from the same (E)-4-(dimethylamino)but-2-enoic acid hydrochloride = EN300-736086 starting material mentioned in the paper, and propose amidation with Nc1c[nH]c2ccccc12 = EN300-342283 and NCc1c[nH]c2ccccc12 = EN300-164849, for 1 and 2 respectively. Thanks for suggesting molecules with a nice route!
(I’ve added the Enamine identifiers because that’s who will likely be making it).