Ethanethiol → 6-fluoro-1-(4-methoxy-benzyl)-1H-pyrido[2,3-d][1,3]oxazine-2,4-dione

反応式

C(S)C.[H-].[Na+].[CH2:6]([O:8][C:9](=[O:30])[C:10]1[CH:15]=[C:14]([F:16])[C:13](SCC)=[N:12][C:11]=1[NH:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)C.C([O:33]C(=O)C1C=C(F)C(SCC)=NC=1Cl)C.C(OC(=O)C1C=C(F)C=NC=1NCC1C=CC(OC)=CC=1)C.ClC(OC(Cl)=O)(Cl)Cl>[Ni].C(O)C>[F:16][C:14]1[CH:13]=[N:12][C:11]2[N:20]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[C:6](=[O:33])[O:8][C:9](=[O:30])[C:10]=2[CH:15]=1

参加物

実験手順

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.

出典と根拠

ORDレコード: ord-8a3fc5ead2f24c1490cff1d80d9a8070
出典データセット: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US07361760B2

反応ノート

読み込み中…

反応式

参加物

反応物 6

生成物 1

試薬・触媒・溶媒 2

実験手順

出典と根拠

反応ノート