06 (brs, 2H, CH2), 5.91 (brs, 2H, 2NH), 6.35 (brs, 2H, arH), 6.83 (brs, 1H, arH), 7.17 (brs, 2H, arH), 7.39 (brs, 2H, arH), 9.56 (brs, 1H, NH), 9.69 (brs, 1H, NH), 10.08 (brs, 1H, NH). 13C NMR (DMSO-d 6, δ ppm): 17.45 (CH3), 43.56 (CH2), 46.49 (CH2), 53.96 (2CH2), 63.67 (CH2), 67.10 (CH2), arC: [105.40 (d, CH, J C–F = 40.1 Hz), 114.19 (CH), 118.62 (d, CH, J C–F = 36.6 Hz), 121.70 (2CH), 124.54 (2CH), 128.55 (d, C, J C–F = 36.4 Hz), 140.19 (d, CH, J C–F = 37.0 Hz), 150.36 (d, C, J C–F = 184.7 Hz), 157.43 (2C)], 168.24 (C=O), 172.66 (C=O), 190.04 (C=S). Ethyl 4-[4-(2-[2-(anilinocarbonothioyl)hydrazino]-2-oxoethylamino)-2-fluorophenyl] piperazine-1-carboxylate (11) The mixture of compound 9 (10 mmol) and phenylisothiocyanate

(10 mmol) BI 6727 supplier in absolute ethanol was heated under Momelotinib reflux for 10 h. On cooling the reaction mixture to room temperature, a white solid appeared. This crude product was filtered off and recrystallized from ethanol. Yield: 85 %, M.p: 160–163 °C. FT-IR (KBr, ν, cm−1): 3340, 3256, 3193 (4NH),

1697 (C=O), 1633 (C=O), NVP-BGJ398 in vitro 1286 (C=S). Elemental analysis for C22H27FN6O3S calculated (%): C, 55.68; H, 5.73, N, 17.71. Found (%): C, 55.98; H, 5.78; N, 17.87. 1H NMR (DMSO-d 6, δ ppm): 1.19 (t, 3H, CH3, J = 7.0 Hz), 2.78 (s, 4H, 2CH2), 3.47 (s, 4H, 2CH2), 3.77 (s, 2H, CH2), 4.04 (q, 2H, CH2, J = 7.2 Hz), 6.34–6.51 (m, 2H, arH), 6.80–6.85 (m, 1H, arH), 7.17 (s, 1H, arH), 7.34–7.38 (d, 4H, arH, J = 8.2 Hz), 9.56 (s, 1H, NH), 9.69 (s, 1H, NH), 10.12 (s, 2H, 2NH). 13C NMR (DMSO-d 6, δ ppm): 15.29 (CH3), 44.25 (CH2), 45.92 (CH2), 51.83 (2CH2), 61.51 (2CH2), arC: [101.29 (d, CH, J C–F = 24.1 Hz), 108.72 (CH), 121.68 (CH), 125.92 (2CH), 126.48 (CH), 128.82 (2CH), 139.70 (C), 146.20 (d, C, J C–F = 10.0 Hz), 154.00 (d, C, J C–F = 63.3 Hz), 157.35 (d, C, J C–F = 209.8 Hz)], 168.64 (C=O), 170.64 (C=O), 181.58 (C=S). MS m/z (%): 475.41 ([M+1]+, 32), 414.53 Thymidylate synthase (26), 413.53 (100), 149.03 (32). Ethyl 4-(4-[(5-anilino-1,3,4-thiadiazol-2-yl)methyl]amino-2-fluorophenyl)piperazine-1-carboxylate

(12) Concentrated sulfuric acid (64 mmol) was added to compound 11 (10 mmol) dropwise while stirring, and the reaction mixture was stirred in an ice bath for 15 min. Then, the mixture was allowed to reach room temperature and stirred for additional 2 h. The resulting solution was poured into ice cold water and made alkaline (pH 8) with ammonia. The precipitated product was filtered, washed with water, and recrystallized from dimethysulfoxide:water (1:3).