p-Toluenesulfonic acid → 2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one

HRID 1498713Notes

Reaction equation

[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[OH:15][C:16]1[C:23]([CH3:24])=[CH:22][C:19]([CH:20]=O)=[CH:18][C:17]=1[CH3:25].OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[OH:15][C:16]1[C:23]([CH3:24])=[CH:22][C:19]([C:20]2[NH:6][C:4](=[O:5])[C:3]3[C:7]([O:13][CH3:14])=[CH:8][C:9]([O:11][CH3:12])=[N:10][C:2]=3[N:1]=2)=[CH:18][C:17]=1[CH3:25]

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of 2-amino-4,6-dimethoxy-nicotinamide (1.40 g, 7.1 mmol) and 4-hydroxy-3,5-dimethylbenzaldehyde (1.07 g, 7.1 mmol) in N,N-dimethyl acetamide (20 mL), NaHSO3 (1.39 g, 7.81 mmol) and p-TSA (0.675 g, 3.55 mmol) were added and the reaction mixture was heated at 150° C. overnight. The solvent was removed under reduced pressure. The residue was diluted with water and the solid was collected and further washed with methanol. The crude product was purified by column chromatography (silica gel 230-400 mesh; 2% methanol in CH2Cl2 as eluent) to give 2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one (0.92 g, 39.6%). Selected data: MS (ES) m/z: 328.07; MP 297-299° C.

Workup

customThe solvent was removed under reduced pressure
additionThe residue was diluted with water
customthe solid was collected
washfurther washed with methanol
customThe crude product was purified by column chromatography (silica gel 230-400 mesh; 2% methanol in CH2Cl2 as eluent)

Sources & evidence

ORD record: ord-c14c5b76ea6c4ccb807e1ab37f39122f
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199990B2

Reaction notes

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