Dimethylformamide → 3-(4-(4-(3,4-Dimethyl-phenyl)piperazin-1-yl)-1,3,5-triazin-2-ylamino)-2-methylbenzamide

Temperature

0 °C

To a solution of 2,4-dichloro-1,3,5-triazine (50.0 mg, 0.333 mmol) in DMF (1334 μL, 0.333 mmol) was added N-ethyl-N-isopropylpropan-2-amine (174 μL, 1.000 mmol). The reaction mixture was cooled in an ice-water bath prior to the addition of 3-amino-2-methylbenzamide (50.1 mg, 0.333 mmol). The reaction mixture was stirred for 1 h at 0° C. at which time LC-MS revealed complete conversion to 3-(4-chloro-1,3,5-triazin-2-ylamino)-2-methylbenzamide. To this yellow solution was added 1-(3,4-dimethylphenyl)piperazine (63.4 mg, 0.333 mmol). The reaction mixture was allowed to stir and warm slowly to RT over 3 h. Water was added yielding a precipitate, which was filtered off, washed with water, and then purified further by reverse phase liquid chromatography using TFA as a modifier. Fractions containing the product were combined and washed with sat. NaHCO3. The product was extracted with CH2Cl2. The organic phase was washed with brine, dried over MgSO4, filtered, and concentrated to afford 3-(4-(4-(3,4-dimethyl-phenyl)piperazin-1-yl)-1,3,5-triazin-2-ylamino)-2-methylbenzamide (78 mg, 0.187 mmol, 56.0% yield) was obtained as a white solid.

1. temperatureThe reaction mixture was cooled in an ice-water bath
2. stirringto stir
3. temperaturewarm slowly to RT over 3 h
4. customyielding a precipitate, which
5. filtrationwas filtered off
6. washwashed with water
7. custompurified further by reverse phase liquid chromatography
8. additionFractions containing the product
9. washwashed with sat. NaHCO3
10. extractionThe product was extracted with CH2Cl2
11. washThe organic phase was washed with brine
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated

ORD record

ord-64143ab4d2c042caa894239489221090

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09334269B2