Ammonium Chloride → tert-butyl 3-(4-amino-1-methyl-1H-pyrazol-5-yl)phenylcarbamate

To a 10 mL microwave vial was added 5-chloro-1-methyl-4-nitro-1H-pyrazole from Example 1 (150 mg, 0.93 mmol), 3-(tert-butoxycarbonylamino)phenylboronic acid (440 mg, 1.86 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (152 mg, 0.019 mmol), a 1:1 M solution of Na2CO3/KOAc (1 mL) and acetonitrile (4 mL). The mixture was irradiated to 130° C. with a microwave for 40 min and the mixture was cooled, concentrated and purified via flash chromatography, heptane/ethyl acetate 20% to 95% to afford a yellow oil. To a 50 mL round bottom flask was added the nitro compound (120 mg, 0.90 mmol), iron (156 mg, 2.8 mmol), ammonium chloride (200 mg, 3.7 mmol), ethanol (10 mL) and water (1.5 mL). The mixture was stirred for 1 h and the reaction was monitored by LCMS. Upon completion of the reaction, the mixture was filtered through a pad of Celite and was washed with ethyl acetate (30 mL) and a 10% aqueous solution of K3PO4 (30 mL). The organic layer was washed with water (30 mL), dried over Na2SO4 and the organic solvent was distilled off to yield tert-butyl 3-(4-amino-1-methyl-1H-pyrazol-5-yl)phenylcarbamate as a brown oil with a purity of >98% (120 mg, 45%) over two steps. ESIMS m/z=289.1 (M+1)

1. customThe mixture was irradiated to 130° C. with a microwave for 40 min
2. temperaturethe mixture was cooled
3. concentrationconcentrated
4. custompurified via flash chromatography, heptane/ethyl acetate 20% to 95%
5. customto afford a yellow oil
6. customUpon completion of the reaction
7. filtrationthe mixture was filtered through a pad of Celite
8. washwas washed with ethyl acetate (30 mL)
9. washThe organic layer was washed with water (30 mL)
10. dry with materialdried over Na2SO4
11. distillationthe organic solvent was distilled off

ORD-Eintrag

ord-0cf21384b7114793ad4cb20befabdc3c

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08614206B2