N,N-Dimethylaniline → 5-Chloro-2-(4-chloro-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile
Reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:21][CH2:20][C:13]3[N:14]=[CH:15][N:16]=[C:17](OC)[C:12]=3[CH2:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8].CN(C)C1C=CC=CC=1.CN(C)C=O.P(Cl)(Cl)([Cl:38])=O.[OH-].[Na+]>C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:21][CH2:20][C:13]3[N:14]=[CH:15][N:16]=[C:17]([Cl:38])[C:12]=3[CH2:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 110 °C
Procedure
A mixture of 5-chloro-2-(4-methoxy-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile (4.15 g, 13.1 mmol), N,N-dimethylaniline (0.18 mL, 1.4 mmol), N,N-dimethylformamide (0.21 mL, 2.7 mmol) and acetonitrile (35 mL) was heated to dissolve at 105° C. Phosphoryl chloride (5.3 mL, 56 mmol) was added dropwise over 3 mins and the mixture was heated to reflux at 110° C. After another 20 hours refluxing, the reaction mixture was allowed to cool and poured over ice (200 g), and then 45% NaOH (75 mL) was added. The mixture was extracted with CH2Cl2 (3×200 mL). The combined organic layers were dried over sodium sulfate, and concentrated. The residue was purified by silica gel chromatography (0-100% EtOAc/hexane) to afford a yellow oil which became a solid in the freezer.
Workup
- temperaturewas heated
- dissolutionto dissolve at 105° C
- temperaturethe mixture was heated
- temperatureAfter another 20 hours refluxing
- temperatureto cool
- extractionThe mixture was extracted with CH2Cl2 (3×200 mL)
- dry with materialThe combined organic layers were dried over sodium sulfate
- concentrationconcentrated
- customThe residue was purified by silica gel chromatography (0-100% EtOAc/hexane)
- customto afford a yellow oil which
Sources & evidence
- ORD record
- ord-7b9135c807ae4a7c87612a29ff2431e8
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08076345B2
Reaction notes
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