3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-2,4-dichloroquinoline → (3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

Temperature

105 °C

A heterogeneous mixture of 2-(4-(1H-pyrazol-1-yl)benzyl)malonic acid (2.42 g 9.29 mmol, Intermediate 4: step b), (4-amino-3-methylphenyl)(1-methyl-1H-imidazol-5-yl)methanone (2 g, 9.29 mmol, Intermediate 13: step c) and POCl3 (10 mL) was heated at 105° C. for 4 hours. The mixture was cooled to room temperature, concentrated to remove excess POCl3 and ice water was added. The mixture was treated with NH4OH (kept adding ice during addition) to a basic pH 8-9 and the aqueous was then extracted with DCM. The DCM extracts were dried (Na2SO4), evaporated in vacuo and chromatographed (DCM/EtOAc, gradient) to provide the crude product. Pure product was precipitated with MeOH, filtered and dried to provide the title compound as a yellow solid.

1. temperatureThe mixture was cooled to room temperature
2. concentrationconcentrated
3. customto remove excess POCl3 and ice water
4. additionwas added
5. additionThe mixture was treated with NH4OH (kept adding ice during addition) to a basic pH 8-9
6. extractionthe aqueous was then extracted with DCM
7. dry with materialThe DCM extracts were dried (Na2SO4)
8. customevaporated in vacuo
9. customchromatographed (DCM/EtOAc, gradient)
10. customto provide the crude product
11. customPure product was precipitated with MeOH
12. filtrationfiltered
13. customdried

ORD record

ord-9dc96d5eaf5b4ab3bc763a0612918907

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221804B2