[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=[NH:31])[NH:7][C:8]1[CH:30]=[CH:29][C:11]2[S:12][CH2:13][CH2:14][N:15]([CH:16]3[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]3)[C:10]=2[CH:9]=1.Cl.C(=O)([O-])[O-].[Na+].[Na+]>CO>[NH:19]1[CH2:18][CH2:17][CH:16]([N:15]2[CH2:14][CH2:13][S:12][C:11]3[CH:29]=[CH:30][C:8]([NH:7][C:6]([C:2]4[S:1][CH:5]=[CH:4][CH:3]=4)=[NH:31])=[CH:9][C:10]2=3)[CH2:21][CH2:20]1To a stirred solution of tert-butyl 4-(6-(thiophene-2-carboximidamido)-2H-benzo[b][1,4]thiazin-4(3H)-yl)piperidine-1-carboxylate (398 mg, 0.868 mmol) in MeOH (6 mL) was added aqueous hydrogen chloride, 3M (2.893 mL, 8.68 mmol). The resulting solution was stirred at 90° C. for 45 minutes The mixture was then cooled to room temperature, basified (pH 12) with saturated sodium carbonate, and then extracted with dichloromethane (3×). The combined organics were dried, filtered, concentrated, and then chromatographed in 1:6 (2M NH3 in MeOH):ethyl acetate to give the desired product 29 (216 mg, 69.4%) as a pale yellow foam. 1H NMR (DMSO-d6) δ 7.71 (d, J=2.7 Hz, 1H), 7.59 (d, J=4.8 Hz, 1H), 7.08 (dd, J=5.1, 3.6 Hz, 1H), 6.86 (d, J=8.1 Hz, 1H), 6.37 (brs, 2H), 6.26 (s, 1H), 6.13-6.08 (m, 1H), 3.68-3.52 (m, 1H), 3.43-3.38 (m, 2H), 3.01-2.93 (m, 4H), 2.61-2.51 (m, 2H), 1.64-1.52 (m, 4H); ESI-MS (m/z, %): 359 (MH+, 100); ESI-HRMS calculated for C18H23N4S2 (MH+), calculated: 359.1358, observed: 359.1351; HPLC purity: 97% by area.
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