3-Hydroxypyridine → 6-chloro-4-(3-pyridinyloxy)-Pyrido[3,2-d]pyrimidine

HRID 1182943Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([OH:7])[CH:2]=1.[H-].[Na+].Cl[C:11]1[C:12]2[N:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:13]=2[N:14]=[CH:15][N:16]=1>CN(C=O)C.O>[Cl:21][C:19]1[CH:18]=[CH:17][C:13]2[N:14]=[CH:15][N:16]=[C:11]([O:7][C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)[C:12]=2[N:20]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of pyridin-3-ol (0.048 g, 0.500 mmol) in DMF (1.67 ml) was added NaH (0.027 g, 55% dispersion in mineral oil, 0.630 mmol) at 0° C. After stiffing for 30 min at room temperature, the reaction mixture was cooled to 0° C. and 4,6-dichloropyrido[3,2-d]pyrimidine (Intermediate 1, step D) (0.1 g, 0.500 mmol) was added to the mixture. After stiffing for 2 hours at room temperature, the reaction mixture was diluted with water, and extracted with EtOAc. The organic layers were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=5:1) to give 6-chloro-4-(pyridin-3-yloxy)pyrido[3,2-d]pyrimidine (0.090 g, 70%) as a white solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 7.46 (1H, dd, J=8.0 and 4.8 Hz), 7.66-7.69 (1H, m), 7.86 (1H, d, J=8.8 Hz), 8.31 (1H, d, J=8.8 Hz), 8.61 (1H, d, J=4.4 Hz), 8.65 (1H, d, J=2.8 Hz), 8.80 (1H, s).

Workup

waitAfter stiffing for 2 hours at room temperature
extractionextracted with EtOAc
dry with materialThe organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=5:1)

Sources & evidence

ORD record: ord-6338c41176dc4767bb4f47cf0b188686
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08664230B2

Reaction notes

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