1-(6-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethan-1-amine → (S)-1-(6-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

참여 물질

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반응 단계

Ortho-chloro-D-tartranilic acid (i.e., (2S,3S)-4-((2-chlorophenyl)amino)-2,3-dihydroxy-4-oxobutanoic acid) (177.5 g, 683.6 mmol) was suspended in water (367 mL) and isopropanol (1.43 L). The mixture was warmed to 40-45° C. over a period of 10 minutes. A solution of 1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethan-1-amine (170 g, 669 mmol) in IPA was added slowly over a period of 10 minutes while maintaining the temperature of the reaction mixture at 35-45° C. The transfer vessel was rinsed with IPA (100 mL). The IPA rinse was added to the reaction mixture, which was then warmed to 80-85° C. and stirred at this temperature for 15 minutes. The mixture was cooled to 70-75° C. over a period of 30 minutes and a seed of ortho-chloro-D-tartranilic acid salt of (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethan-1-amine (350 mg) was added. The reaction mixture was maintained at 70-75° C. for an additional 20 minutes before cooling the mixture to 60-65° C. over a period of 45 minutes. The reaction mixture was maintained at 60-65° C. with stirring for 2 hours before slowly cooling the mixture to 20° C. over a period of 9 hours. The mixture was stirred for 8 hours at 20° C. and then filtered. The solid product was washed with IPA/water (9:1 v/v, 2×510 mL) and then re-suspended in IPA/water (9:1 v/v, 1.19 L). The mixture was warmed to 40-45° C. and maintained at this temperature for 2 hours. The suspension was slowly cooled to 20° C. over a 1 hour period and maintained at 20° C. for 1.5 hours. The reaction mixture was filtered, washed with IPA/water (9:1 v/v, 595 mL), and dried under vacuum at 40° C. to give ortho-chloro-D-tartranilic acid salt of the title compound as a white solid (115.3 g, 99.1% de, 99.6% purity by HPLC).

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