Dimethylformamide → Methyl 4-amino-3-fluorobenzoate

A 100 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with the product of Step 4 (2.3 g, 8.3 mmol) and N,N-dimethyl formamide (20 mL). 1,8-diazabicyclo[5.4.0]undec-7-ene (1.4 mL, 9.1 mmol) was added followed by 2,4-difluorobenzyl bromide (1.2 mL, 9.1 mmol). The reaction mixture was stirred at 60 C. for 3 h, was poured into saturated aqueous NaHCO3 and was extracted with ethyl acetate. The organic layer was washed with brine and concentrated in vacuo. The solid was triturated with acetonitrile and filtered to give the title compound (2.15 g, 64%). 1H NMR (400 MHz, CD3OD) δ 7.99 (dd, J=1.7 and 8.4 Hz, 1H), 7.93 (dd, J=1.8 and 10.4 Hz, 1H), 7.55 (m, 1H), 7.48 (t, J=6.8 Hz, 1H), 7.02 (m, 2H), 6.18 (dd, J=1.3 and 2.76 Hz, 1H), 6.02 (d, J=2.7 Hz, 1H), 5.14 (s, 2H), 3.94 (s, 3H), 1.98 (s, 3H) ppm. 19F NMR (400 MHz, CD3OD) δ−111.34 (1 F), −115.97 (1 F), −122.98 (1 F) ppm. ES-HRMS m/z 404.1133 (M+H calcd for C21H17F3NO4 requires 404.1104). Step 5 Preparation of methyl 4-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-3-fluorobenzoate

1. customA 100 mL round bottomed flask equipped with stirbar and nitrogen inlet
2. extractionwas extracted with ethyl acetate
3. washThe organic layer was washed with brine
4. concentrationconcentrated in vacuo
5. customThe solid was triturated with acetonitrile
6. filtrationfiltered

ORD record

ord-246bf1f04b954d30b581eeb070ebbe8d

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067540B2