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CAS No. : | 58421-80-0 | MDL No. : | MFCD08457971 |
Formula : | C9H7ClN2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | UTBDPFFXKANFFT-UHFFFAOYSA-N |
M.W : | 178.62 | Pubchem ID : | 18185618 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H319 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With trichlorophosphate; at 120℃; for 12h;Inert atmosphere; | Phosphorous oxychloride (800 mL) was taken in a 2 L round bottom flask under nitrogen. To this was added 8-Methylquinazolin-4(3H)-one (125 g) in portions. The reactionminxture refluxed at 120 C for 12h. Reaction completion was monitored by TLC and LCMS. After completion, the reactionminxture was cooled to RT and evaporated to dryness under reduced pressure. The resulted residue was dissolved in DCM (500 mL) and quenched slowly into an ice cold solution of saturated K2C03 with constant stirring. Then the organic layer was separated and washed with brine solution, dried over sodium sulfate and concentrated under vacuum to afford 4-chloro-8-methylquinazoline (120 g, 86%) as yellow solid. This was taken for next step without further purification. MS: m/z = 179/18 1 [M+Hj. |
35% | With trichlorophosphate; In acetonitrile;Reflux; | b. Preparation of Compound 12b To a solution of 8-methylquinazolin-4(3H)-one 12a (1.1 g, 6.92 mmol) in 155 ml ACN was added 10.1 mL POCl3. The reaction mixture is refluxed until completion, cooled to room temperature. The solvent was removed under vacuum, and the crude product was purified in ISCO using Ethyl acetate: hexane solvent system to afford the pure product (430 mg, 35% yield). 1H NMR (CDC13, 400 MHz) delta 9.06 (s, 1H), 8.12 (d, J= 8.4 Hz, 1H), 7.80 (d, J = 6.9 Hz, 1H), 7.61 (m, 1H), 2.78 (s, 3H). |
35% | With trichlorophosphate; In acetonitrile;Reflux; | To a solution of 8-methylquinazolin-4(3H)-one 12a (1.1 g, 6.92 mmol) in 155 ml ACN was added 10.1 mE P0C13. The reaction mixture is refluxed until completion, cooled to room temperature. The solvent was removed under vacuum, and the crude product was purified in ISCO using Ethyl acetate:hexane solvent system to afford the pure product (430 mg, 35% yield). 1H NMR (CDCl3, 400 MHz) oe 9.06 (s, 1-H), 8.12 (d, J=8.4 Hz, 1H), 7.80 (d, J=6.9 Hz, 1-H), 7.61 (m, 1H), 2.78 (s, 3H). |
With trichlorophosphate; at 120℃; for 12h;Inert atmosphere; | POCI3 (300 mL) was taken in a 2 L round bottom flask under nitrogen. To this was added 8-Methylquinazolin-4(3H)-one (45 g) in portions. The reaction mixture refluxed at 120 C for 12h. Reaction completion was monitored by TLC and LCMS. After completion, the reaction mixture was cooled to RT and evaporated to dryness under reduced pressure. The resulted residue was dissolved in DCM (500 mL) and quenched slowly into an ice cold solution of saturated K2C03 with constant stirring. Then the organic layer was separated and washed with brine solution, dried over sodium sulphate and concentrated under vacuum to afford (45g, 90% yield) of the titled compound as yellow solid. This was taken for next step without further purification. H NMR (CDCI3, 400MHz) delta 9.03 (s, 1 H), 8.08-8.06 (dd, J = 8.9, 8.4 Hz, 1 H), 7.77-7.76 (d, J = 7.1 Hz, 1 H), 7.59-7.56 (d, J = 15.5 Hz, 1 H), 2.75 (s, 3H). | |
With thionyl chloride; N,N-dimethyl-formamide; for 8h;Reflux; | General procedure: A mixture of 4-quinazolone analogues 2a-2j (8.0 mmol) in SOCI2 (27.4 mL) containing DMF (2 drops) was refluxed for 8 h. SOCI2 was removed under reduced pressure and the residue was dissolved in DCM. The solution was washed with saturated NaHCO3 solution and brine, respectively, dried over anhydrous Na2S04 and then concentrated under reduced pressure to yield the compounds 3a-3j (65.1-88.9percent yield) as white or off-white solid. | |
With thionyl chloride; In N,N-dimethyl-formamide; for 5h;Reflux; | General procedure: A mixture of 4-hydroxyquinazoline (0.02 mol) in SOCl2 (20 mL)containing DMF (2 drops) was refluxed for 5 h. SOCl2 was removedunder reduced pressure, and the residue was dissolved in dichloromethane(DCM). The solution was washed with NaHCO3 solutionand brine, dried over anhydrous Na2SO4, and concentrated under reducedpressure to obtain the desired compound as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With thionyl chloride; N,N-dimethyl-formamide;Reflux; | General procedure: 6,7-Dimethoxyquinazolin-4(3H)-one (20 g, 9.7 mmol) and 0.1 mL of /V,//-dimethylformamide were added to 50 mL of thionyl chloride. The resulting mixture was stirred at reflux for overnight. After cooled to room temperature, the solvent was removed in vacuo and saturated sodium carbonate solution was added to adjust the pH value to 8 at 0 C. The resulting mixture was extracted with dichloromethane and the combined organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1) to give 1.96 g (88%) of the tilte compound as a yellow solid. MS (ESIpos): m/z = 225 (M+H)+; LC-MS [Method 1] : Rt = 0.91 min. |
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