Diphenyl carbonate → Phenyl 7-(dimethoxymethyl)-6-((N-methylacetamido)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

HRID 1777912Notes

Reaction equation

[CH3:1][O:2][CH:3]([O:20][CH3:21])[C:4]1[C:13]([CH2:14][N:15]([CH3:19])[C:16](=[O:18])[CH3:17])=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1.[C:22](=O)([O:30]C1C=CC=CC=1)[O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH4+].[Cl-]>C1COCC1>[CH3:21][O:20][CH:3]([O:2][CH3:1])[C:4]1[N:5]=[C:6]2[C:11]([CH2:10][CH2:9][CH2:8][N:7]2[C:22]([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:30])=[CH:12][C:13]=1[CH2:14][N:15]([CH3:19])[C:16](=[O:18])[CH3:17]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of N-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N-methylacetamide (intermediate 115) (470 mg, 1.282 mmol) and diphenyl carbonate (288 mg, 1.346 mmol) in THF (5 mL) was slowly added 1.6M LHMDS in THF (1.202 mL, 1.923 mmol) at −78° C. The reaction mixture was stirred at −78° C. for 30 min, then left to warm to room temperature. The reaction mixture was poured into saturated NH4Cl solution. The aqueous was extracted with DCM (×2). The combined organic extracts were concentrated under reduced pressure. Purification of the crude product by chromatography on silica eluting with 0-100% EtOAc in heptane afforded Phenyl 7-(dimethoxymethyl)-6-((N-methylacetamido)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate. UPLC-MS 3 Rt=0.89 min; MS m/z [M+H]+ 414.3.

Workup

customat −78° C
waitleft
temperatureto warm to room temperature
extractionThe aqueous was extracted with DCM (×2)
concentrationThe combined organic extracts were concentrated under reduced pressure
customPurification of the crude product by chromatography on silica eluting with 0-100% EtOAc in heptane

Sources & evidence

ORD record: ord-03ad5bf2aedd4be1ad37518b8e8dbd28
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266883B2

Reaction notes

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