Triethylamine → 3-(5-Iodo-pyridin-2-yloxy)-azetidine-1-carboxylic acid pyridin-3-ylamide

2-(Azetidin-3-yloxy)-5-iodo-pyridine hydrochloride (4.2 g, 13 mmol) was suspended in anhydrous dichloromethane (50 mL) and triethylamine (5.5 mL) was added. Pyridine-3-isocyanate (1.45 g, 11.7 mmol) was added and the reaction mixture was stirred at ambient temperature for 16 hr. The suspension solvents were removed in vacuo and the residue partitioned between ethyl acetate (400 mL) and sat. aqueous sodium bicarbonate solution (400 mL). The mixture was filtered through a pad of celite and the filtrate phases were separated. The organic phase was washed with sat. aqueous sodium bicarbonate solution (250 mL), then sat aqueous sodium chloride solution (250 mL) and dried over sodium sulphate and filtered. The filtrate solvents were removed in vacuo to afford a yellow solid which was purified by flash chromatography on silica gel (100 g), eluting with a 1:19 mix of 7N ammonia in methanol solution:dichloromethane. This affords the title compound (2.0 g, 42%) as a colourless solid.

1. customThe suspension solvents were removed in vacuo
2. customthe residue partitioned between ethyl acetate (400 mL) and sat. aqueous sodium bicarbonate solution (400 mL)
3. filtrationThe mixture was filtered through a pad of celite
4. customthe filtrate phases were separated
5. washThe organic phase was washed with sat. aqueous sodium bicarbonate solution (250 mL)
6. dry with materialdried over sodium sulphate
7. filtrationfiltered
8. customThe filtrate solvents were removed in vacuo
9. customto afford a yellow solid which
10. customwas purified by flash chromatography on silica gel (100 g)
11. washeluting with a 1:19
12. additionmix of 7N ammonia in methanol solution

ORD record

ord-ca325c9cb40e443abcd2842f04424566

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006269B2