Phosphorus oxychloride → 6-(8-chloro-3-methyl-1,7-naphthyridin-4-yl)-N-methylquinazolin-2-amine
Reaction equation
[CH3:1][C:2]1[CH:3]=[N:4][C:5]2[C:6](=O)[NH:7][CH:8]=[CH:9][C:10]=2[C:11]=1[C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[C:17]([NH:22][CH3:23])[N:16]=[CH:15]2.P(Cl)(Cl)([Cl:27])=O>>[Cl:27][C:6]1[N:7]=[CH:8][CH:9]=[C:10]2[C:5]=1[N:4]=[CH:3][C:2]([CH3:1])=[C:11]2[C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[C:17]([NH:22][CH3:23])[N:16]=[CH:15]2Participants
Conditions
- Temperature
- 100 °C
Procedure
A mixture of 3-methyl-4-(2-(methylamino)quinazolin-6-yl)-1,7-naphthyridin-8(7H)-one (0.400 g, 1.26 mmol) and phosphorous oxychloride (5.00 ml, 1.26 mmol) was heated to 100° C. After 3 hours, the volatiles were removed under vacuum. Residual phosphorous oxychloride was azeotroped with toluene. The resulting residue was dissolved in chloroform and washed with cold water. The organic layer was then washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was then dried with sodium sulfate and purified by column chromatography on silica gel using a gradient of 50 to 100% EtOAc in hexanes to give 6-(8-chloro-3-methyl-1,7-naphthyridin-4-yl)-N-methylquinazolin-2-amine as a yellow solid. MS(M+H)+ 336.
Workup
- customthe volatiles were removed under vacuum
- customResidual phosphorous oxychloride was azeotroped with toluene
- dissolutionThe resulting residue was dissolved in chloroform
- washwashed with cold water
- washThe organic layer was then washed (2×) with an aqueous saturated solution of sodium bicarbonate
- dry with materialThe organic layer was then dried with sodium sulfate
- custompurified by column chromatography on silica gel using a gradient of 50 to 100% EtOAc in hexanes
Sources & evidence
- ORD record
- ord-480a04e94c79404d978dd8940b763c69
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08440674B2
Reaction notes
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