Tetrahydrofuran → 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-(propan-2-yloxy)-3,4-dihydro-2,6-naphthyridin-1(2H)-one

HRID 577544Notes

Reaction equation

[Cl:1][C:2]1[C:3]([O:13][CH:14]([CH3:16])[CH3:15])=[N:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2.[CH2:17]([O:24][C:25]1[C:30]([CH2:31]Cl)=[C:29]([CH3:33])[CH:28]=[C:27]([CH3:34])[N:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1COCC1>O1CCOCC1>[CH2:17]([O:24][C:25]1[C:30]([CH2:31][N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[C:2]([Cl:1])[C:3]([O:13][CH:14]([CH3:16])[CH3:15])=[N:4][CH:5]=3)[C:10]2=[O:12])=[C:29]([CH3:33])[CH:28]=[C:27]([CH3:34])[N:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of 8-chloro-7-(propan-2-yloxy)-3,4-dihydro-2,6-naphthyridin-1(2H)-one (112e, 60.0 mg, 0.250 mmol) and 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 78 mg, 0.3 mmol) in 1,4-dioxane (3 mL) was added KHMDS in THF (1.0 M, 1.24 mL, 1.24 mmol). The reaction mixture was heated at 100° C. for 1 hour, then cooled to room temperature. The reaction mixture was concentrated, H2O (10 mL) was added, and the aqueous layer extracted with EtOAc (3×10 mL). The combined organic layers were concentrated under vacuum and the residue purified by preparative HPLC to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-(propan-2-yloxy)-3,4-dihydro-2,6-naphthyridin-1(2H)-one (112f, 22 mg, 19% yield) as a white solid.

Workup

temperaturecooled to room temperature
concentrationThe reaction mixture was concentrated
additionH2O (10 mL) was added
extractionthe aqueous layer extracted with EtOAc (3×10 mL)
concentrationThe combined organic layers were concentrated under vacuum
customthe residue purified by preparative HPLC

Sources & evidence

ORD record: ord-ea766ae539a541fe9e783aebd41a0ba4
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040515B2

Reaction notes

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