Methyl iodide → HCID 67536344, compound

Temperature

200 °C

The intermediate, cyclopropyl-(5-nitro-pyridin-2-yl)-amine, from the above procedure, was methylated with methyl iodide. To a 2 mL microwave vial was added cyclopropyl-(5-nitro-pyridin-2-yl)-amine (146 mg, 0.812 mmol), DMF (2 mL), potassium carbonate (224 mg, 1.62 mmol), and the MeI (56 μl, 0.893 mmol). The mixture was heated by microwave for two 10 min increments at 200° C. using a Personal Chemistry, Emrys Optimizer. Then followed addition of another portion of MeI (56 μL, 0.893 mmol) microwave at 200° C. for 10 min and then conventional heating at 70° C. for 15 hr. At the end of this period a third addition of MeI (56 μL, 0.893 mmol) took place and the mixture was heated by microwave once more for 10 min at 200° C. The reaction mixture was then concentrated to dryness, suspended in ethyl acetate (100 mL) and washed with water (100 mL) two times and one time with brine. The aqueous layers were combined and extracted once with ethyl acetate (50 mL). The combined organic layer was washed once with brine (100 mL), concentrated, supported onto silica gel, and purified by flash chromatography using the Analogix system with a 12 g Silicycle silica gel column with increasing concentrations of ethyl acetate in hexanes (20 mL/min, equilibrate with 0%, 0 to 5 min: 0%; 5 to 25 min: 0 to 30%; 25-45 min: 30%). The appropriate fractions were collected and dried to afford 90 mg of cyclopropyl-methyl-(5-nitro-pyridin-2-yl)-amine, a yellow solid (yield 57%). LCMS calcd. for C9H11N3O2 (m/e) 193, observed 194 (M+H). This intermediate nitropyridyl compound was then reduced, as described in the preparation of cyclopentyl-pyridine-2,5-diamine above, to afford N2-cyclopropyl-N2-methyl pyridine-2,5-diamine. LCMS calcd. for C9H13N3 (m/e) 163, observed 164 (M+H).

1. temperatureconventional heating at 70° C. for 15 hr
2. temperaturethe mixture was heated by microwave once more for 10 min at 200° C
3. concentrationThe reaction mixture was then concentrated to dryness
4. washwashed with water (100 mL) two times and one time with brine
5. extractionextracted once with ethyl acetate (50 mL)
6. washThe combined organic layer was washed once with brine (100 mL)
7. concentrationconcentrated
8. custompurified by flash chromatography
9. temperaturewith increasing concentrations of ethyl acetate in hexanes (20 mL/min, equilibrate with 0%, 0 to 5 min: 0%; 5 to 25 min: 0 to 30%; 25-45 min: 30%)
10. customThe appropriate fractions were collected
11. customdried

ORD record

ord-ffe4748fc97f4659b5594639075b36c5

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07714126B2