反应详情

4-[3-(4-tert-Butoxycarbonylamino-pyridin-3-yl)-propenyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester from EXAMPLE 96, Part B (45 mg, 0.10 mmol) is dissolved in 20% TFA/CH2Cl2 and stirred at r.t. for 2 hours. The solution is concentrated to residue. The residue is dissolved in MeCN (2.5 ml) and treated with 4-methylmorphorline (0.027 ml, 0.25 mmol). 2-(5-Chloro-thiophen-2-yl)-ethenesulfonyl chloride (24 mg, 0.10 mmol), EXAMPLE 3, in MeCN (1 mL) is then added dropwise. The reaction mixture is stirred at r.t. for 1 h, then subjected to reverse phase HPLC purification, to give the title compound as white solid (0.040 g, 0.037 mmol). MS m/z 439, 441 (M+H); 1H NMR (CD3OD, 300 MHz) δ8.20 (br, 1H), 8.10 (s, 1H), 8.08 (d, 1H), 7.60 (d, 1H), 7.53 (d. 1H), 7.35 (d, 1H), 7.21 (d, 1H), 7.07 (d, 1H), 6.82 (d, 1H), 5.27 (m, 1H), 3.88 (s, 2H), 3.60-3.50 (m, 4H), 3.30 (d, 2H).

1. concentrationThe solution is concentrated to residue
2. dissolutionThe residue is dissolved in MeCN (2.5 ml)
3. additiontreated with 4-methylmorphorline (0.027 ml, 0.25 mmol)
4. stirringThe reaction mixture is stirred at r.t. for 1 h
5. customphase HPLC purification