1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 7-{(2E)-4-[tert-Butyl(methyl)amino]but-2-enoyl}-4-[(3-chloro-4-fluorophenyl)amino]-5,6,7,8-tetrahydrothieno[2,3-b:5,4-c']dipyridine-3-carbonitrile

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Reaction Steps

(2E)-4-Bromobut-2-enoic acid (100 mg, 0.61 mmol) and tert-butyl methylamine (60 mg, 0.67 mmol) were dissolved in DCM (3.0 mL). DIPEA (94 mg, 0.73 mmol) was added, and the mixture was heated overnight to 50° C. After cooling to rt, the compound of Example 55A (75 mg, 0.21 mmol), DCM (1.0 mL), EDCI (48 mg, 0.25 mmol) and DIPEA (32 mg, 0.25 mmol) were added, and the mixture was stirred at rt overnight. Subsequently, it was diluted with water, and the mixture was extracted three times with DCM. The combined organic layers were dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by preparative HPLC to yield 41 mg (37%) of the title compound.

Provenance & Evidence