3-Methoxyazetidine hydrochloride → (S)-1-(6-(3-Methoxyazetidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

Temperature

90 °C

To a microwave vial containing 3-methoxyazetidine hydrochloride (500 mg, 4.05 mmol) were added KOt-Bu (1339 mg, 11.93 mmol) and DME (8 mL) under an atmosphere of nitrogen. The mixture was heated to 90° C. in a sand bath. A solution of (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (461 mg, 1.82 mmol) in DME (8 mL) was added dropwise to the hot suspension. The mixture was stirred at 90° C. overnight. Additional KOt-Bu (1956 mg, 17.43 mmol) was added and the mixture was heated to 90° C. for 90 minutes. The reaction mixture was subsequently concentrated in vacuo. The residue was dispersed in DMSO/MeOH (1:1, 10 mL), filtered, and purified by preparative HPLC eluting with 15-40% ACN in water (with 0.035% NH4HCO3). The fractions containing the desired product were combined and concentrated in vacuo to give the title compound as an off-white solid (469 mg, 99%). ESI-MS m/z [M+H]+ calc'd for C14H20N4O, 261; found 261.

1. temperaturethe mixture was heated to 90° C. for 90 minutes
2. concentrationThe reaction mixture was subsequently concentrated in vacuo
3. additionThe residue was dispersed in DMSO/MeOH (1:1, 10 mL)
4. filtrationfiltered
5. custompurified by preparative HPLC
6. washeluting with 15-40% ACN in water (with 0.035% NH4HCO3)
7. additionThe fractions containing the desired product
8. concentrationconcentrated in vacuo

ORD record

ord-4d4b304724464bb5b6c571b454c01692

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08835420B2