Hydrochloric Acid → 3-acetyl-4-amino-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-1-methyl-1,8-naphthyridin-2(1H)-one

HRID 13803

Reaction equation

[C:1]([C:4]1[C:5](=[O:34])[N:6]([CH3:33])[C:7]2[C:12]([C:13]=1[NH:14]C(=O)C)=[CH:11][C:10]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=1)=[C:9]([C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=1[Cl:32])[N:8]=2)(=[O:3])[CH3:2].Cl>O1CCOCC1.CCOC(C)=O>[C:1]([C:4]1[C:5](=[O:34])[N:6]([CH3:33])[C:7]2[C:12]([C:13]=1[NH2:14])=[CH:11][C:10]([C:18]1[CH:19]=[CH:20][C:21]([Cl:24])=[CH:22][CH:23]=1)=[C:9]([C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=1[Cl:32])[N:8]=2)(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 50 °C

Procedure

To 16 mg of the product of Example 1 in 1,4-dioxane (1 mL) was added 0.5 mL of 1 M aqueous HCl solution. The reaction stirred at 50° C. for 5 hours. LC/MS indicated little product forming and an additional 0.2 mL of concentrated HCl solution was added. The temperature was increased to 90° C. for 4.5 hours at which point the reaction was cooled to room temperature and diluted with EtOAc. The solution was washed with saturated aqueous NaHCO3 solution before drying with Na2SO4 and concentrating. The residue was purified by preparative TLC (silica gel) eluted with 20% EtOAc in CH2Cl2 affording the title compound. HPLC/MS: 471.9 (M+1), 473.9 (M+3); Rt=4.32 min.

Workup

customforming
temperatureThe temperature was increased to 90° C. for 4.5 hours at which
temperaturewas cooled to room temperature
washThe solution was washed with saturated aqueous NaHCO3 solution
dry with materialbefore drying with Na2SO4
concentrationconcentrating
customThe residue was purified by preparative TLC (silica gel)
washeluted with 20% EtOAc in CH2Cl2 affording the title compound

Sources & evidence

ORD record: ord-c547244f2ee541b2b0328425718be039
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07728141B2

Linked notes

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