Dichloromethane → Bis(cyclopropylmethyl)amine

To a suspension (3-{[(3,5-bistrifluoromethyl-benzyl)-(2H-tetrazol-5-yl)-amino]-methyl}-8-methyl-quinolin-2-yl)-bis-cyclopropylmethyl-amine (0.132 g, 0.224 mmol) in water (2 mL), sodium hydroxide (0.018 g, 0.448 mmol) was added and stirred for 15 min at RT followed by the addition of dichloromethane (2 mL). To this reaction mixture, dimethyl sulphate (0.032 g, 0.26 mmol) was added followed by the addition of tetra butyl ammonium bromide (0.003 g, 0.011 mmol). The reaction was stirred for 1 h. The organic layer was separated from aqueous layer and the aqueous layer was extracted with DCM (3×10 mL), the combined organic layer was washed with brine, dried over sodium sulphate and then concentrated under vacuum to afford the crude residue which was purified by column chromatography over 100-200 mesh silica gel using 8% ethyl acetate and petroleum ether to afford (3-{[3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazole-5-yl)-amino]-methyl-}-8-methyl-quinoline-2-yl)-bis-cyclopropylmethyl-amine (0.07 g, 52%).

1. stirringThe reaction was stirred for 1 h
2. customThe organic layer was separated from aqueous layer
3. extractionthe aqueous layer was extracted with DCM (3×10 mL)
4. washthe combined organic layer was washed with brine
5. dry with materialdried over sodium sulphate
6. concentrationconcentrated under vacuum
7. customto afford the crude residue which
8. customwas purified by column chromatography over 100-200 mesh silica gel using 8% ethyl acetate and petroleum ether

ORD record

ord-e877775c9e884da0b09183885e311e38

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604055B2