6,10-Dioxa-2-azaspiro[4.5]decane → 1-(2,4-Difluorophenyl)-7-(1,5-dioxa-8-azaspiro[5.4]dec-8-yl)-6-fluoro-1,8-naphthyridine-3-carboxylic acid
Reaction equation
[O:1]1[C:6]2([CH2:10][CH2:9][NH:8][CH2:7]2)[O:5][CH2:4][CH2:3][CH2:2]1.C([O:13][C:14]([C:16]1[CH2:17][N:18]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[F:35])[C:19]2[C:24]([CH:25]=1)=[CH:23][C:22]([F:26])=[C:21](Cl)[N:20]=2)=[O:15])C>>[F:35][C:29]1[CH:30]=[C:31]([F:34])[CH:32]=[CH:33][C:28]=1[N:18]1[C:19]2[C:24](=[CH:23][C:22]([F:26])=[C:21]([N:8]3[CH2:9][CH2:10][C:6]4([O:5][CH2:4][CH2:3][CH2:2][O:1]4)[CH2:7]3)[N:20]=2)[CH:25]=[C:16]([C:14]([OH:15])=[O:13])[CH2:17]1Participants
3
Conditions
- Temperature
- 45 °C
Procedure
Following the procedure of Step 2 Example 331 a 0.168 g (1.17 mmol) of 1,5-dioxa-8-azaspiro[5.4]decane, from Step 2 Example 14, was reacted with 0.300 g (0.78 mmol) of 1-(2,4-difluorophenyl)-7-chloro-6-fluoro-1,8-naphthyridine-3-carboxylic acid ethyl ester by heating at 40° C. instead of 45° C. for 10 instead of 24 hours. The solvent was removed by evaporation to afford the title product which was purified by column chromatography over silica gel (0% increasing to 4% methanol/methylene chloride) to afford 0.252 g of the title compound. The ester was not further purified, but was taken directly to the next step.
Workup
- customThe solvent was removed by evaporation
Sources & evidence
- ORD record
- ord-52c9154fdfca406b8dc6ee68491ad955
- Source dataset
- uspto-grants-1992_08
- Patent number
- US05137892
Reaction notes
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