Data were recorded using MP100, Biopac digital acquisition system, www.selleckchem.com/products/ABT-263.html and analyzed using Acknowledge 3.5.7 software (Biopac). Synthesis procedures Flash chromatography was performed on a CombiFlash Companion chromatography system (Teledyne Isco, Lincoln, NE). 1H and 13C NMR images were obtained on a Bruker 300 MHz instrument (Bruker Corp., Billerica, MA, USA). High-resolution mass spectrometry was done at a core facility at the University of California (Riverside, CA, USA). Elemental analyses were done at the Micro-Mass Facility (University of California, Berkeley, CA, USA). N-(2-methoxyethyl)-4-phenyl-2-thiazolamine (compound 1) A solution of 2-bromoacetylphenone (1.59 g, 7.99 mmol) and 1-(2-methoxyethyl)-2-thiourea (1.02 g, 7.61 mmol) in ethanol (30 ml) was refluxed under argon for 4 h.
After the reaction mixture was cooled to room temperature, saturated aqueous NaHCO3 was slowly added. Ethanol was removed under reduced pressure. The resulting suspension was extracted twice with CH2Cl2. The combined organic phase was washed with water, dried (Na2SO4), and concentrated. Chromatography [silica, hexanes:ethyl acetate (9:1 to 4:1)] yielded a white crystalline solid (1.62 g, 91%), melting point 57�C60��C. 1H NMR (300 MHz, CDCl3) �� 3.39 (s, 3H), 3.53 (m, 2H), 3.64 (m, 2H), 5.46 (br, 1H), 6.70 (s, 1H), 7.27 (m, 1H), 7.37 (m, 2H), and 7.80 (m, 2H). 13C NMR (75 mHz, CDCl3) �� 45.2, 58.8, 70.7, 101.0, 126.0, 127.6, and 128.5. ESI-MS calculated for C12H15N2OS 235.0900; found 235.0902. N-(2-methoxyethyl)-N-(4-phenyl-2-thiazolyl)-2,3,4-trimethoxybenzeneacetamide (Eact) A solution of compound 1 (1.
00 g, 4.27 mmol) and anhydrous pyridine (690 ml, 8.54 mmol) in anhydrous toluene (40 ml) was stirred for 5 min. To the reaction mixture was added a solution of 3,4,5-trimethoxybenzoyl chloride (1.47 g, 6.41 mmol) in anhydrous toluene (20 ml). The mixture was refluxed under argon for 4.5 h, cooled to room temperature, and poured into water and ethyl acetate. The organic phase was collected, dried (Na2SO4) and concentrated. Chromatography [silica, hexanes:ethyl acetate (4:1 to 3:1)] yielded a crystalline solid (1.33 g, 73%), melting point 97�C100��C. 1H NMR (300 MHz, CDCl3) �� 3.28 (s, 3H), 3.86 (t, J = 5.4, 2H), 3.88 (s, 6H), 3.90 (s, 6H), 4.48 (t, J = 5.4, 2H), 6.92 (s, 2H), 7.26 (s, 1H), 7.33 (m, 1H), 7.43 (m, 2H), and 7.90 (m, 2H). 13C NMR (75 mHz, CDCl3) �� 49.
6, 56.2, 58.9, 61.0, 69.7, 105.4, 109.4, 126.0, 127.9, and 128.7. ESI-MS is calculated for C22H25N2O5S 429.1479; found 429.1477. Synthesis of Fact analogs, exemplified with N-(4-bromophenyl)-3-(1H-tetrazol-1-yl)benzamide (Fact) Thionyl chloride (477 ml, 6.58 mmol) and 3-(1H-tetrazol-1-yl)benzoic acid (50 mg, 0.263 Dacomitinib mmol) was heated to 80��C in a screw-cap vial. After a clear solution was observed, the residue solid on the wall was washed by gentle shaking. After 1.5 h, the reaction was cooled to room temperature.