Diisopropylamine → 3-Ethynyl-6-methoxymethyl-pyridin-2-ylamine

Temperature

-78 °C

To a mixture of diisopropylamine (0.15 mL) and THF (2 mL) was added n-butyl lithium (1.6M n-hexane solution, 0.68 mL) by drops at −78° C., which was stirred for 30 minutes at the same temperature. Trimethylsilyldiazomethane (2M n-hexane solution, 0.50 mL) was added to the reaction mixture at −78° C., which was stirred for 30 minutes at the same temperature. 2-Amino-6-methoxymethyl-pyridin-3-carbaldehyde (150 mg) described in Manufacturing Example 19-2 and THF (1.5 mL) were added by drops to the reaction mixture at −78° C., which was stirred for 30 minutes at 0° C. The reaction mixture was cooled to −78° C., after which a mixture of acetic acid (0.10 mL) and THF (1 mL) was added by drops thereto. The reaction mixture was gradually raised to 0° C., and was extracted using water and ethyl acetate. The organic layer was washed with saturated brine and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=2:3) to obtain the titled compound (73 mg).

1. stirringwhich was stirred for 30 minutes at the same temperature
2. additionwere added by drops to the reaction mixture at −78° C.
3. stirringwhich was stirred for 30 minutes at 0° C
4. additionwas added by drops
5. temperatureThe reaction mixture was gradually raised to 0° C.
6. extractionwas extracted
7. washThe organic layer was washed with saturated brine
8. customthe solvent was evaporated under a reduced pressure
9. customThe residue was purified by silica gel column chromatography (ethyl acetate:heptane=2:3)

ORD record

ord-ca559d387b6c4238ba40bf7a53838049

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08183264B2