Ethyl orthoformate → 2-Cyanoethyl 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate

HRID 2090207Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:17](=[O:19])[NH:16][CH:15]=[C:14]([CH3:20])[C:13]=3[NH:12][C:11]([CH3:21])=[C:10]2[C:22]([O:24][CH2:25][CH2:26][C:27]#[N:28])=[O:23])=[C:5]([O:29][CH3:30])[CH:4]=1)#[N:2].C(OCC)(OCC)O[CH2:33][CH3:34]>S(=O)(=O)(O)O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:13](=[C:14]([CH3:20])[CH:15]=[N:16][C:17]=3[O:19][CH2:33][CH3:34])[NH:12][C:11]([CH3:21])=[C:10]2[C:22]([O:24][CH2:25][CH2:26][C:27]#[N:28])=[O:23])=[C:5]([O:29][CH3:30])[CH:4]=1)#[N:2]

Participants

Conditions

Temperature: 130 °C

Procedure

2.22 g (5.44 mmol) of the compound from Example 28A are suspended in 100 ml of triethyl orthoformate and heated to 130° C. Then, over a total period of 8 hours, 10 drops of concentrated sulfuric acid are added each hour to the reaction mixture. It is then stirred at the same temperature overnight. After cooling, excess orthoester is removed in a rotary evaporator, and the crude product is purified by column chromatography (silica gel; mobile phase: initially dichloromethane then isohexane/ethyl acetate 1:1). The product fractions are combined, the solvent is removed, and the residue is crystallized from ethyl acetate/diethyl ether. The precipitate is filtered off and dried under high vacuum. 1.80 g (77% of theory) of the title compound are obtained.

Workup

temperatureAfter cooling
customexcess orthoester is removed in a rotary evaporator
customthe crude product is purified by column chromatography (silica gel
customthe solvent is removed
customthe residue is crystallized from ethyl acetate/diethyl ether
filtrationThe precipitate is filtered off
customdried under high vacuum

Sources & evidence

ORD record: ord-23bb161b57e247ef88686f7ec692f9cc
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08436180B2

Reaction notes

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