Diisopropylethylamine → N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide

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Reaction Steps

DIPEA (16.83 g, 130.2 mmol) was added to a suspension of H2NMe.HCl (5.02 g, 74.4 mmol) in THF (180 mL) and stirred at room temperature for 0.5 h. 2-((2-Chloro-4-(dimethylcarbamoyl)phenyl)(methyl) carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylic acid (9.00 g, 18.6 mmol) and HATU (21.22 g, 55.8 mmol) were added into the suspension separately. The reaction mixture was stirred at room temperature for 2 h. Concentrated to remove solvent, the resulting mixture was dissolved in CH2Cl2 (200 mL), washed by 2N HCl (200 mL), water (100 mL), and dried over Na2SO4. The crude product was purified by silica gel chromatography eluted with CH2Cl2:MeOH=10:1 (3.70 g, 40%) to furnish 223. ESI-MS: 498. 1H NMR (CDCl3, 400 MHz): δ7.58 (s, 1H, ArH), 7.42-7.29 (m, 4H, ArH), 6.92 (s, 1H, ArH), 6.34 (d, J=4.0 Hz, 1H, NH), 4.20 (t, J=5.0 Hz, 2H, CH2), 3.37 (s, 3H, CH3), 3.12 (s, 3H, CH3), 3.04-2.98 (m, 8H, CH2, 2CH3).

Provenance & Evidence