Ammonium Chloride → 7-(Dimethoxymethyl)-1,2,3,4-tetrahydro-6-methoxy-1,8-naphthyridine

HRID 1778044Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[CH:12]([O:15][CH3:16])[O:13][CH3:14])[NH:8][CH2:7][CH2:6][CH2:5]2.[CH3:17][O-:18].[Na+].[NH4+].[Cl-]>CO>[CH3:14][O:13][CH:12]([O:15][CH3:16])[C:11]1[N:10]=[C:9]2[C:4]([CH2:5][CH2:6][CH2:7][NH:8]2)=[CH:3][C:2]=1[O:18][CH3:17]

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of 6-bromo-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 2, 253 mg, 0.881 mmol) in MeOH (0.85 ml) under argon was treated with NaOMe (5.4 M in MeOH, 0.816 ml, 4.41 mmol), flushed with argon, treated with CuBr (253 mg, 1.76 mmol). The vial was sealed and the reaction mixture was stirred at 120° C. for 15 h. The reaction mixture was cooled to room temperature, treated with sat. aq. NH4Cl and extracted with EtOAc (2×). The combined org. layers were washed again with brine, dried over Na2SO4 and concentrated. 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 pale yellow oil. (UPLC-MS 1) tR 0.73 min; ESI-MS 239.1 [M+H]+.

Workup

customflushed with argon
customThe vial was sealed
temperatureThe reaction mixture was cooled to room temperature
extractionextracted with EtOAc (2×)
washlayers were washed again with brine
dry with materialdried over Na2SO4
concentrationconcentrated
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-89570f4291d04e2b9e11c6be48626c99
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266883B2

Reaction notes

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