2-Amino-5-cyanopyridine → N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777847Notes

Reaction equation

[CH3:1][O:2][CH:3]([O:23][CH3:24])[C:4]1[N:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][N:11]2[C:14]([O:16]C2C=CC=CC=2)=O)=[CH:6][CH:5]=1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][N:27]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[C:32]([C:29]1[CH:30]=[CH:31][C:26]([NH:25][C:14]([N:11]2[C:12]3[C:7](=[CH:6][CH:5]=[C:4]([CH:3]([O:2][CH3:1])[O:23][CH3:24])[N:13]=3)[CH2:8][CH2:9][CH2:10]2)=[O:16])=[N:27][CH:28]=1)#[N:33]

Participants

Conditions

Temperature: -15 °C

Procedure

A solution of phenyl 7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 3, 262 mg, 0.798 mmol) and 2-amino-5-cyanopyridine (190 mg, 1.60 mmol) in THF (7.5 ml) at −15° C. under argon was treated drop wise with LHMDS (1M in THF, 1.60 ml, 1.60 mmol). The reaction mixture was stirred at −15° C. for 25 min and then quenched by addition of sat. aq. NH4Cl and extracted with EtOAc (2×). The combined org. layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100) to give the title compound as a white solid. (UPLC-MS 1) tR 1.09 min; ESI-MS 354.1 [M+H]+.

Workup

customquenched by addition of sat. aq. NH4Cl
extractionextracted with EtOAc (2×)
washlayers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100)

Sources & evidence

ORD record: ord-ef5855163c3f4edd88b169593ce7dce6
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266883B2

Reaction notes

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