Phosphorus oxychloride → 7-Benzyl-4-chloro-2-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine
Reaction equation
[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14](=O)[NH:13][C:12]([CH3:19])=[N:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:22])=O>>[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([Cl:22])=[N:13][C:12]([CH3:19])=[N:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
Procedure
7-Benzyl-2-methyl-5,6,7,8-tetrahydro-3H-pyrido[3,4-d]pyrimidin-4-one (prepared according to the method of Example 86, Step A, 17.1 g, 67.0 mmol) was suspended in phosphorus oxychloride (66 mL, 335 mmol). This mixture was stirred at reflux for 1 h, cooled to room temperature, evaporated, then chased with toluene. The residue was carefully diluted with ice/water/chloroform and the layers were separated. The aqueous phase was extracted with chloroform (3×) and the combined organic extracts were washed with saturated aqueous sodium bicarbonate (1×) and water (1×), dried over sodium sulfate, filtered, and evaporated to give the title compound of Example 86, Step B as a brown oil that was used without purification in the next step. 1H NMR (CDCl3, 250 MHz) δ 7.36-7.23 (c, 5H), 3.73 (s, 2H), 3.63 (s, 2H), 2.63 (app s, 4H), 2.36 (s, 3H); MS (APCI) 274, 276 (MH+).
Workup
- temperatureat reflux for 1 h
- customevaporated
- additionThe residue was carefully diluted with ice/water/chloroform
- customthe layers were separated
- extractionThe aqueous phase was extracted with chloroform (3×)
- washthe combined organic extracts were washed with saturated aqueous sodium bicarbonate (1×) and water (1×)
- dry with materialdried over sodium sulfate
- filtrationfiltered
- customevaporated
Sources & evidence
- ORD record
- ord-82f6765ea7c349e18a8300c5f364c747
- Source dataset
- uspto-grants-2003_12
- Patent number
- US06660740B1
Reaction notes
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