[CH3:1][S:2][C:3]1[S:7]C(C(OC)=O)=[CH:5][C:4]=1[C:12](=O)NCC(=O)C1C=CC=CC=1.COC(C1SC(C)=C(C(O)=S)C=1)=O.C(Cl)(=O)C([Cl:40])=O.[NH2:43][CH2:44][C:45]([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:46].C([N:56]([CH2:60][CH3:61])C(C)C)(C)C.C[N:63](C=O)C>C(Cl)Cl>[ClH:40].[CH3:1][S:2][C:3]1[S:7][C:61]([C:60]([NH2:56])=[NH:63])=[CH:5][C:4]=1[C:12]1[O:46][C:45]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[CH:44][N:43]=1Methyl 5-methylthio-4-[N-(2-oxo-2-phenylethyl)carbamoyl]thiophene-2-carboxylate: To a stirred suspension of 300 mg (1.29 mmol) of 5-(methoxycarbonyl)-2-methylthiothiophene-3-carboxylic acid (as prepared in Example 95) in 10 mL of anhyd CH2Cl2 (under a CaSO4 drying tube) was added 135 μL (1.55 mmol) of oxalyl chloride followed by 30 μL of anhyd DMF. After stirring for 2 h at room temperature, the mixture was concentrated in vacuo. The resulting yellow solid was dissolved in 10 mL of anhyd CH2Cl2, cooled (0° C.) and 266 mg (1.55 mmol) of 2-aminoacetophenone was added. N,N-diisopropylethylamine (DIEA) (756 μL, 4.34 mmol) was added dropwise over 3 min and the mixture stirred for 1 h at room temperature. The mixture was concentrated to an oil and partitioned between 125 mL of EtOAc and 80 mL of 1 M HCl. The aqueous layer was extracted with ethyl acetate (2×30 mL) and the combined organic phases were washed with 1 M HCl (60 mL), saturated NaHCO3 (120 mL), and brine (120 mL) and dried over Na2SO4. After removing the solvent in vacuo, the residue was recrystallized from MeOH to afford the title compound as a cream-colored powder (314 mg, 70%). 1H-NMR (300 MHz, DMSO-d6) δ 8.82 (t, 1H, J=6 Hz), 8.43 (s, 1H), 8.02 (d, 2H, J=7 Hz), 7.69 (t, 1H, J=7 Hz), 7.57 (t, 2H, J=7 Hz), 4.72 (d, 2H, J=6 Hz), 3.84 (s, 3H) and 2.57 (s, 3H). Mass spectrum (MALDI-TOF, α-cyano-4-hydroxycinnamic acid matrix) calcd. for C16H15NO4S2: 372.0 (M+Na). Found: 372.1.
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