Hydrochloric Acid → HCID 44612632, compound

Temperature

125 °C

Int-1 (1.99 g, 0.016 mmol) and Int-2 (1.85 mL, 0.016 mol) were dissolved in NMP (15 mL) and the resulting mixture was heated under microwave condition with stirring at 125° C. for 40 minutes. It was then diluted with EtOAc and washed with saturated aqueous NaHCO3 solution. The organic layers were then combined and dried with MgSO4. Filtration and concentration gave Int-3 (2.92 g). MS m/z: 209 (MH+). Crude Int-3 (2.92 g) and DMF-DMA (5 mL) were dissolved in DMF (10 mL), and heated under microwave condition with stirring at 160° C. for 20 minutes. The precipitate formed was then collected by filtration to afford Int-4 (1.53 g, 37% for two steps). MS m/z: 264 (MH+). A mixture of Int-4 (1.53 g, 5.8 mmol), Int-5 (1.670 g, 8.6 mol) and DBU (1.72 mL, 11.6 mol) in DMF (15 mL) was heated under microwave condition with stirring at 160° C. After 30 minutes, water was added. The precipitate formed was collected by filtration and washed with water to afford Int-6 (1.20 g, 53%). MS m/z: 394 (MH+). A solution of Int-6 (0.15 g, 0.4 mmol) and dimethylaminoethanol (0.5 mL) in NMP (4 mL) was treated with KOtBu (0.200 g, 1.78 mmol) and heated under microwave condition with stirring at 170° C. After 10 minutes, water was added to the reaction mixture and acidified to about pH 4 with 1N HCl. The precipitate formed was collected by filtration to afford Int-7 (0.13 g, 80%). MS m/z: 433 (MH+). Int-7 (0.13 g, 0.3 mmol) was coupled with phenylenediamine (0.035 g, 0.3 mmol) in the presence of HATU (0.15 g, 0.4 mmol) and triethylamine (0.12 mL, 0.9 mmol) in DMF (2 mL) and then purified by preparative HPLC to afford the title compound. MS (C29H30N8O2) m/z: 523 (MH+). NMR 1H NMR (dmso-d6): δ 10.12 (s, 1H), 9.74 (s, 1H), 9.64 (d, J=7.2 Hz, 1H), 8.67 (d, J=5.2 Hz, 1H), 7.94 (d, J=8.8 Hz, 2H), 7.86 (d, J=8.8 Hz, 2H), 7.25 (s, 1H), 7.20 (d, J=5.2 Hz, 2H), 7.05 (m, 2H), 6.95 (m, 1H), 6.82 (m, 1H), 4.54 (s, 2H), 3.57 (s, 2H), 2.85 (s, 6H), 2.66 (s, 3H), 2.49 (s, 2H).

1. temperaturethe resulting mixture was heated under microwave condition
2. washwashed with saturated aqueous NaHCO3 solution
3. dry with materialdried with MgSO4
4. filtrationFiltration and concentration
5. customgave Int-3 (2.92 g)
6. temperatureheated under microwave condition
7. stirringwith stirring at 160° C. for 20 minutes
8. customThe precipitate formed
9. filtrationwas then collected by filtration
10. customto afford Int-4 (1.53 g, 37% for two steps)
11. temperaturewas heated under microwave condition
12. stirringwith stirring at 160° C
13. waitAfter 30 minutes
14. customThe precipitate formed
15. filtrationwas collected by filtration
16. washwashed with water
17. customto afford Int-6 (1.20 g, 53%)
18. temperatureheated under microwave condition
19. stirringwith stirring at 170° C
20. waitAfter 10 minutes
21. customThe precipitate formed
22. filtrationwas collected by filtration
23. customto afford Int-7 (0.13 g, 80%)
24. custompurified by preparative HPLC

ORD record

ord-14105df5025648f49230d77fd2545158

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08124764B2