Sodium hydride → 6-chloro-4-[(1-methyl-4-piperidinyl)oxy]-Pyrido[3,2-d]pyrimidine

HRID 1182941Notes

Reaction equation

HRID 1182941 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.[H-].[Na+].Cl[C:12]1[C:13]2[N:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:14]=2[N:15]=[CH:16][N:17]=1>CN(C=O)C.O>[Cl:22][C:20]1[CH:19]=[CH:18][C:14]2[N:15]=[CH:16][N:17]=[C:12]([O:8][CH:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)[C:13]=2[N:21]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 660484-Piperidinol, 1-methyl-HCID 105841654,6-Dichloropyrido[3,2-d]pyrimidine2×

Product 1

HCID 866710666-chloro-4-[(1-methyl-4-piperidinyl)oxy]-Pyrido[3,2-d]pyrimidineYield 43.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-methylpiperidin-4-ol (0.095 g, 0.825 mmol) in DMF (2.500 ml) was added NaH (0.041 g, 55% dispersion in mineral oil, 0.945 mmol) at 0° C. After stirring for 30 min at room temperature, the reaction mixture was cooled to 0° C., followed by the addition of 4,6-dichloropyrido[3,2-d]pyrimidine (Intermediate 1, step D) (0.15 g, 0.750 mmol). 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-(1-methylpiperidin-4-yloxy)pyrido[3,2-d]pyrimidine (0.09 g, 43%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 2.03-2.12 (2H, m), 2.17-2.21 (2H, m), 2.22-2.32 (2H, m), 2.34 (3H, s), 2.84-2.89 (2H, m), 5.38-5.45 (1H, m), 7.73 (1H, d, J=8.8 Hz), 8.18 (1H, d, J=8.8 Hz), 8.81 (1H, s).

Workup

  1. temperaturethe reaction mixture was cooled to 0° C.
  2. waitAfter stiffing for 2 hours at room temperature
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=5:1)

Sources & evidence

ORD record
ord-fe0f576428794580907d0ac0f595a172
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

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