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0 °C

tert-butyl (3R,4R)-4-(6-carbamoyl-5-(6-methylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (60 mg, 83% pure, 0.112 mmol) was dissolved in dichloromethane (0.85 mL) and cooled to 0° C. Trifluoroacetic acid (0.35 mL, 4.49 mmol) was added drop-wise, then the mixture was warmed to room temperature. After 3 h, the mixture was concentrated in vacuo then water, sodium bicarbonate solution and ethyl acetate were added. The aqueous phase was extracted with ethyl acetate. Sodium chloride was added to the aqueous layer and it was further extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by chromatography (silica, 0-10% methanol in dichloromethane) gave 6-((3R,4R)-3-amino-tetrahydropyran-4-ylamino)-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (11 mg, 28%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 11.61 (s, 1H) 8.39 (br. s., 1H) 8.12 (s, 1H) 7.65 (br. s., 1H) 7.60 (t, J=7.7 Hz, 1H) 6.95 (d, J=7.2 Hz, 1H) 6.85 (d, J=7.6 Hz, 1H) 6.75 (d, J=8.3 Hz, 1H) 4.10 (br. s., 1H) 3.79-3.89 (m, 1H) 3.66-3.75 (m, 1H) 3.49-3.57 (m, 1H) 3.37-3.47 (m, 1H) 3.00-3.08 (m, 1H) 1.94-2.12 (m, 1H) 1.76-1.92 (m, 1H) 1.63-1.73 (m, 1H). MS (EI/CI) m/z: 344 [M+H].

1. temperaturethe mixture was warmed to room temperature
2. concentrationthe mixture was concentrated in vacuo
3. additionwater, sodium bicarbonate solution and ethyl acetate were added
4. extractionThe aqueous phase was extracted with ethyl acetate
5. additionSodium chloride was added to the aqueous layer and it
6. extractionwas further extracted with ethyl acetate
7. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customPurification by chromatography (silica, 0-10% methanol in dichloromethane)