2-Methoxybenzylamine → 9-(4-Methoxy-benzylamino)-5H-benzo[c][1,8]naphthyridin-6-one

HRID 1029082Notes

Reaction equation

Cl[C:2]1[CH:16]=[CH:15][C:5]2[C:6](=[O:14])[NH:7][C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[CH:10][N:9]=3.CO[C:19]1[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=1[CH2:21][NH2:22].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C[C:62](C)([O-:64])C.[Na+]>O1CCOCC1.CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:62][O:64][C:25]1[CH:26]=[CH:19][C:20]([CH2:21][NH:22][C:2]2[CH:16]=[CH:15][C:5]3[C:6](=[O:14])[NH:7][C:8]4[C:13]([C:4]=3[CH:3]=2)=[CH:12][CH:11]=[CH:10][N:9]=4)=[CH:23][CH:24]=1

Participants

Conditions

Temperature: 100 °C

Procedure

9-Chloro-5H-benzo[c][1,8]naphthyridin-6-one (40 mg, 0.17 mmol), 2-methoxy-benzylamine (36 mg, 0.26 mmol), palladium(II) acetate (2 mg, 0.01 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (7 mg, 0.02 mmol), and sodium tert-butoxide (50 mg, 0.52 mmol) were suspended in dioxane (1 mL), and stirred overnight at 100° C. The reaction mixture was diluted with MeOH, filtered through a filter membrane, and purified via prep-LC-MS. The recovered product was converted to the HCl salt via suspending in CH2Cl2, addition of 2 M HCl/ether, filtering the resulting precipitate, and washing with CH2Cl2 to provide 33 (10 mg, 16% yield) as a yellow solid. LC-MS (M+H=332, obsd.=332). 1H NMR (400 MHz, d6-DMSO): δ 11.48 (s, 1H), 8.53 (dd, 1H), 8.42 (dd, 1H), 7.98 (d, 1H), 7.39 (d, 1H), 7.32 (dd, 1H), 7.25 (m, 2H), 7.03 (d, 1H), 6.91 (m, 2H), 4.43 (s, 2H), 3.88 (s, 3H).

Workup

filtrationfiltered through a filter membrane
custompurified via prep-LC-MS
additionaddition of 2 M HCl/ether
filtrationfiltering the resulting precipitate
washwashing with CH2Cl2

Sources & evidence

ORD record: ord-5087a83ba7584bc792a80e9ecf0813fd
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08735584B2

Reaction notes

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