[CH2:1]([NH:4][C:5]([C:7]1[S:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=1[Cl:19])=O)[CH:2]=[CH2:3].C(Cl)Cl.P(Cl)(Cl)(Cl)(Cl)Cl.Cl.CO[CH:32](OC)[CH2:33][NH2:34].O1CCOCC1>O1CCOCC1>[CH2:1]([N:4]1[CH:32]=[CH:33][N:34]=[C:5]1[C:7]1[S:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=1[Cl:19])[CH:2]=[CH2:3]To a solution of N-allyl-3-(2,4-dichlorophenyl)thiophene-2-carboxamide (8.60 g, 27.5 mmol) in DCM (309 mL, 4820 mmol) was added phosphorus pentachloride (6.54 g, 31.4 mmol) and 4 M hydrochloric acid in 1,4-dioxane (0.51 mL, 2.00 mmol) and the mixture was heated to 60° C. for 2 hrs. The reaction was cooled to room temperature and aminoacetaldehyde dimethyl acetal (33.9 mL, 311 mmol) was slowly added. The resulting mixture was heated at 60° C. for 2.5 hrs. To the reaction mixture was added 4 M hydrochloric acid in 1,4-dioxane (200 mL, 783 mmol) and the mixture was stirred at 60° C. overnight. After cooling to room temperature, the suspension was filtered through a Celite pad and the solid residue was washed with 1,4-dioxane. The filtrate was evaporated down and the resulting residue was dissolved in water (300 mL) and extracted with EtOAc (2×150 mL). The water layer was basified by addition of solid NaHCO3 until pH 9, and the aqueous was extracted with EtOAc (3×300 mL). All organics were combined and dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, elution with 8-25% EtOAc in DCM) to give crude product which was further purified by column chromatography (SiO2, elution with 45% MeCN: 50% DCM: 5% EtOAc) to provide 7.12 g of product (76%). LC/MS (FA), ES+ 337. 1H NMR (400 MHz, d6 DMSO) δ: 7.80 (d, J=5.3 Hz, 1H,), 7.68 (d, J=2.0 Hz, 1H), 7.35 (dd, J=2.0, 8.3 Hz, 1H), 7.26 (d, J=5.3 Hz, 1H), 7.13 (d, J=1.3 Hz, 1H), 7.08 (d, J=8.3 Hz, 1H), 6.98 (d, J=1.3 Hz, 1H), 5.47-5.58 (m, 1H), 4.98-5.02 (m, 1H), 4.75-4.82 (m, 1H), 4.19-4.23 (m, 2H).
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