Thionyl Chloride → Ethyl 2,6-dichloro-5-fluoropyridine-3-carboxylate
Reaction equation
[Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].N1C2C(=CC=CN=2)C=[CH:15][CH:14]=1.S(Cl)(Cl)=O>C(O)C>[CH2:14]([O:5][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([F:12])[C:9]([Cl:11])=[N:10][C:2]=1[Cl:1])[CH3:15]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
2,6 Dichloro-5-fluoro-nicotinic acid was selected as a starting material to make the compounds of structure (Ia) with fluoro substitution at 6-position of naphthyridine moiety. 2,6 Dichloro-5-fluoro-nicotinic acid was esterified by treating with thionyl chloride followed by refluxing with dry ethanol to yield 2,6-dichloro-5-fluoro-nicotinic acid ethyl ester, depicted by formula 21 in Scheme 10. This ester gave 2-chloro-6-ethylsulfanyl-5-fluoro-nicotinic acid ethyl ester, depicted by formula 22 in Scheme 10, when reacted with ethanethiol and sodium hydride. 6-Ethylsulfanyl-5-fluoro-2-(4-methoxy-benzylamino)-nicotinic acid ethyl ester, depicted by formula 23 in Scheme 10, was prepared by amination of 2-chloro-6-ethylsulfanyl-5-fluoro-nicotinic acid ethyl ester, which was converted into 5-fluoro-2-(4-methoxy-benzylamino)-nicotinic acid ethyl ester, depicted by formula 24 in Scheme 10, by refluxing with ethanol and raney nickel. 5-Fluoro-2-(4-methoxy-benzylamino)-nicotinic acid ethyl ester was then reacted with trichloromethylchloroformate to yield 6-fluoro-1-(4-methoxy-benzyl)-1H-pyrido[2,3-d][1,3]oxazine-2,4-dione, depicted by formula 25 in Scheme 10. The sequence of reactions is shown in Scheme 10.
Sources & evidence
- ORD record
- ord-f7e75018610b4dcc8f251c25ae419568
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07361760B2
Reaction notes
Loading…