Hydrazine hydrate (1:1) → tert-butyl (6-(((2S)-2-acetamidopropyl)oxy)-5-fluoropyridin-3-yl)carbamate
Reaction equation
[O:1]=[C:2]1[C:10]2C(=CC=CC=2)C(=O)[N:3]1[C@@H:12]([CH3:30])[CH2:13][O:14][C:15]1[N:20]=[CH:19][C:18]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:17][C:16]=1[F:29].O.NN>C1COCC1>[C:2]([NH:3][C@@H:12]([CH3:30])[CH2:13][O:14][C:15]1[N:20]=[CH:19][C:18]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[CH:17][C:16]=1[F:29])(=[O:1])[CH3:10]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
A mixture of tert-butyl (6-(((2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl)oxy)-5-fluoropyridin-3-yl)carbamate (1.62 g), hydrazine monohydrate (0.976 g) and THF (15 mL) was stirred overnight at 60° C. The precipitate was removed by filtration, and the obtained filtrate was concentrated under reduced pressure. The obtained residue was mixed with acetic anhydride (0.736 mL), triethylamine (1.09 mL) and ethyl acetate (15 mL), and the obtained mixture was stirred at 60° C. for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (1.05 g).
Workup
- customThe precipitate was removed by filtration
- concentrationthe obtained filtrate was concentrated under reduced pressure
- additionThe obtained residue was mixed with acetic anhydride (0.736 mL), triethylamine (1.09 mL) and ethyl acetate (15 mL)
- stirringthe obtained mixture was stirred at 60° C. for 1 hr
- concentrationThe reaction mixture was concentrated under reduced pressure
- customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
Sources & evidence
- ORD record
- ord-0762b2c0dbb046fe878589dd5b0b725c
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09133129B2
Reaction notes
Loading…