1,2-Dichloroethane → Morpholine-2-carboxamide

To a solution of (1S,3R)—N1-[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]cyclohexane-1,3-diamine (0.06 g, 0.12 mmol) in CH2Cl2 (3 mL) was added 4-tert-butoxycarbonylmorpholine-2-carboxylic acid (40.4 mg, 0.17 mmol), EDC (0.03 g, 0.14 mmol), HOBt (0.02 g, 0.12 mmol) and iPr2NEt (0.06 g, 0.47 mmol), and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure, and the residue was dissolved in CH2Cl2 (2 mL) and TFA (2 mL) and allowed to stir at room temperature for 2 hours. The resulting solution was concentrated in vacuo, dissolved in THF (4 mL) and treated with 1N aqueous lithium hydroxide (3.0 mL, 3.0 mmol). The reaction mixture was heated in the microwave to 130° C. for 20 min. The solvent was evaporated under reduced pressure, and the residue was purified by HPLC, using 5-70% MeOH/H2O with 6 mM HCl over 15 minutes. The purified fractions were concentrated to provide the bis-hydrochloride of N-[(1R,3S)-3-[[2-(5-chloro-1H-pyrrolo[2, 3-1)]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]cyclohexyl]morpholine-2-carboxamide.

1. customThe solvent was evaporated under reduced pressure
2. dissolutionthe residue was dissolved in CH2Cl2 (2 mL)
3. stirringto stir at room temperature for 2 hours
4. concentrationThe resulting solution was concentrated in vacuo
5. dissolutiondissolved in THF (4 mL)
6. temperatureThe reaction mixture was heated in the microwave to 130° C. for 20 min
7. customThe solvent was evaporated under reduced pressure
8. customthe residue was purified by HPLC
9. customover 15 minutes
10. concentrationThe purified fractions were concentrated

ORD record

ord-55cf0865b1be4f10bc79a598eca25a6f

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08829007B2