HCID 136400729, compound → HCID 58948128, compound

Temperature

150 °C

1-Benzyl-4-benzylamino-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid (1-hydroxyimino-ethyl)-amide was suspended in toluene and sealed in a microwave vial (Biotage, 0.5-2.0 ml). The vial was sealed and heated under microwave irradiation (Biotage Initiator 8) for 15 minutes at 150° C. Sample heated in microwave for a further 30 minutes at 150° C., and again for a further 30 minutes at 150° C. The mixture was evaporated then partitioned between EtOAc (10 ml) and water (5 ml). The aqueous was extracted twice more with EtOAc (2×10 ml) then the combined organics were dried (MgSO4) and evaporated. The residue was suspended in acetonitrile (2 ml) and this mixture was sealed in a microwave vial then heated under microwave irradiation for 30 minutes at 170° C., then at 190° C. for a further 30 minutes. The reaction mixture was concentrated in vacuo then dissolved in concentrated H2SO4 (2 ml). The solution was left to stir for 30 minutes then poured onto crushed ice. A saturated aqueous K2CO3 solution was added drop-wise until pH was ˜8. The aqueous was decanted from the solid into a separating funnel then extracted with EtOAc (3×15 ml). The combined organics were dried (MgSO4) and evaporated. The mixture of isomers was purified by HPLC on a Luna 10 micron C18(2) column (150×21.2 mmid). Eluted with 0.1% formic acid (aq) and 0.1% formic acid in MeCN at a flow rate of 25 ml/min. The gradient was isocratic at 5% organic for 0.6 minutes, then increased linearly from 5% to 90% organic over 8.50 minutes. The desired fractions were evaporated to give the title compound as a white solid (0.5 mg, 1%). LCMS Rt=2.46 m/z 323 [MH]+

1. customsealed in a microwave vial (Biotage, 0.5-2.0 ml)
2. customThe vial was sealed
3. customThe mixture was evaporated
4. customthen partitioned between EtOAc (10 ml) and water (5 ml)
5. extractionThe aqueous was extracted twice more with EtOAc (2×10 ml)
6. dry with materialthe combined organics were dried (MgSO4)
7. customevaporated
8. customthis mixture was sealed in a microwave
9. temperatureheated under microwave irradiation for 30 minutes at 170° C.
10. waitat 190° C. for a further 30 minutes
11. concentrationThe reaction mixture was concentrated in vacuo
12. dissolutionthen dissolved in concentrated H2SO4 (2 ml)
13. waitThe solution was left
14. additionthen poured
15. customonto crushed ice
16. additionA saturated aqueous K2CO3 solution was added drop-wise until pH was ˜8
17. customThe aqueous was decanted from the solid into a separating funnel
18. extractionthen extracted with EtOAc (3×15 ml)
19. dry with materialThe combined organics were dried (MgSO4)
20. customevaporated
21. additionThe mixture of isomers
22. customwas purified by HPLC on a Luna 10 micron C18(2) column (150×21.2 mmid)
23. washEluted with 0.1% formic acid (aq) and 0.1% formic acid in MeCN at a flow rate of 25 ml/min
24. waitThe gradient was isocratic at 5% organic for 0.6 minutes
25. temperatureincreased linearly from 5% to 90% organic over 8.50 minutes
26. customThe desired fractions were evaporated

ORD record

ord-8f23e36c43204dbd9edf43e825724c87

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07691877B2