Cl.[NH2:2][OH:3].[OH-].[K+].NO.[K].[CH3:9][C:10]1[C:14]2[CH2:15][N:16]([C:19]([C:21]3[N:22]([CH3:26])[CH:23]=[CH:24][CH:25]=3)=[O:20])[CH2:17][CH2:18][C:13]=2[S:12][C:11]=1[C:27]([O:29]CC)=O.C(O)=O>CO.CS(C)=O>[OH:3][NH:2][C:27]([C:11]1[S:12][C:13]2[CH2:18][CH2:17][N:16]([C:19]([C:21]3[N:22]([CH3:26])[CH:23]=[CH:24][CH:25]=3)=[O:20])[CH2:15][C:14]=2[C:10]=1[CH3:9])=[O:29]
A mixture of hydroxylamine hydrochloride (2 g, 29 mmol) in methanol (10 mL) was heated at 90° C. under a dry nitrogen atmosphere until homogenous. To the heated solution was added a solution of potassium hydroxide (2.85 g, 50.8 mmol) in methanol (6 mL). The formation of a white precipitate was observed. After heating at 90° C. for 30 minutes, the mixture was cooled to room temperature and the solids allowed to settle. The resulting solution was assumed to have a 1.7 M concentration of hydroxylamine•potassium salt and was carefully removed by syringe to exclude solids. An aliquot of the above solution (1 mL, 1.7 mmol) was added to a solution of ethyl 3-methyl-5-(1-methyl-1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate obtained in the previous step dissolved in methanol (1 mL). After stirring for 30 minutes at room temperature, the reaction was quenched with the addition of formic acid (0.1 mL, 3 mmol). The reaction mixture was concentrated to dryness and the residue obtained redissolved in DMSO (1 mL) and purified by reverse phase Gilson prep-HPLC to afford the title compound as a white solid (7.2 mg, 22.5% over two steps). LCMS (FA) ES+ 320; 1H NMR (400 MHz, DMSO) δ 6.93-6.92 (m, 1H), 6.44 (dd, J=3.8, 1.6 Hz, 1H), 6.06 (dd, J=3.7, 2.6 Hz, 1H), 4.55 (s, 2H), 3.88 (t, J=5.6 Hz, 2H), 3.67 (s, 3H), 2.88 (d, J=2.8 Hz, 2H), 2.22 (s, 3H).
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