Water → 5-Bromo-3-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-2-pyridinamine
Reaction equation
[NH2:1][C:2]1[N:10]=[CH:9][C:8]([Br:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH:12]1([C:15]([NH:17][NH2:18])=O)[CH2:14][CH2:13]1.O.C([O-])(O)=O.[Na+]>O=P(Cl)(Cl)Cl>[Br:11][C:8]1[CH:7]=[C:3]([C:4]2[O:6][C:15]([CH:12]3[CH2:14][CH2:13]3)=[N:17][N:18]=2)[C:2]([NH2:1])=[N:10][CH:9]=1Participants
Conditions
- Temperature
- 0 °C
Procedure
A solution of 2-amino-5-bromo-nicotinic acid (300 mg, 1.38 mmol) and cyclopropanecarboxylic acid hydrazide (300 mg, 3.0 mmol) in POCl3 (30.0 mL) was stirred for 18 h at 65° C. The reaction mixture was distilled under reduced pressure to obtain a residue, which was cooled to 0° C. by adding iced water and neutralizing with saturated NaHCO3 solution (100 mL). The aqueous layer was extracted with ethyl acetate. The ethyl acetate layer was separated, dried over anhydrous Na2SO4 and evaporated to afford 370 mg of crude 5-bromo-3-(5-cyclopropyl-[1,3,4]oxadiazol-2-yl)-pyridin-2-ylamine. Crude compound was purified by column chromatography using silica gel (100-200 mesh). The column was eluted with 15% EtOAc in petroleum ether to afford the title compound as a pale yellow solid used without further purification.
Workup
- distillationThe reaction mixture was distilled under reduced pressure
- customto obtain a residue, which
- extractionThe aqueous layer was extracted with ethyl acetate
- customThe ethyl acetate layer was separated
- dry with materialdried over anhydrous Na2SO4
- customevaporated
Sources & evidence
- ORD record
- ord-d17bdb5eb4ec463e8aacfec3c16f4c1e
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09321748B2
Reaction notes
Loading…