Urea → HCID 23449997, compound

To a 250 mL round bottomed flask was charged 2.0 g of 2-fluoro-3-methoxy-benzoic acid in 80 mL of anhydrous toluene. Triethylamine (1.15 eq, 1.88 mL) was added after drying over molecular sieves. After dropwise addition of diphenylphosphoryl azide (1.15 eq, 2.8 mL) in 12 mL toluene, the reaction was stirred for 20 minutes at ambient temperature. The reaction was heated to 95° C., then stirred for 20 minutes. After the reaction was cooled to ambient temperature, 1,2-diamino-2-methyl-propane (1.15 eq, 1.42 mL) was added in 20 mL CH2Cl2. Urea formation was complete in 2 hours. The reaction mixture was diluted with 100 mL H2O and extracted with EtOAc (3×100 mL). The combined organics were washed with brine (1×100 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was filtered over a pad of silica (65×40 mm), impurities eluted with 100%EtOAc, the product eluted with 50%MeOH/CH2Cl2. The eluent was concentrated in vacuo to yield 1.85 g (62%) of 1-(2-Amino-2-methyl-propyl)-3-(2-fluoro-3-methoxy-phenyl)-urea as a brown solid. 1H NMR (CDCl3) δ: 7.61 (dt,1H), 7.0 (dt,1H), 6.61 (dt,1H), 5.75 (bs,1H), 3.87 (s,3H), 3.14 (d,2H), 1.12 (s,6H); MS (CI) m/z 256 (MH+).

1. customafter drying over molecular sieves
2. temperatureThe reaction was heated to 95° C.
3. stirringstirred for 20 minutes
4. temperatureAfter the reaction was cooled to ambient temperature
5. extractionextracted with EtOAc (3×100 mL)
6. washThe combined organics were washed with brine (1×100 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. filtrationThe residue was filtered over a pad of silica (65×40 mm), impurities
11. washeluted with 100%EtOAc
12. washthe product eluted with 50%MeOH/CH2Cl2
13. concentrationThe eluent was concentrated in vacuo

ORD record

ord-d28639c14b5d4f7f8752d11f30969416

Source dataset

uspto-grants-2004_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06677340B2