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

HRID 555524Notes

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-e866a958a0e74fb9896ca7e247405448
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08053440B2

Reaction notes

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