6-Aminonicotinic acid → 6-Amino-5-bromo-nicotinic acid

Bromine (2.3 mL, 44.6 mmol) was added dropwise to a suspension of the 6-aminonicotinic acid Compound 112a (5.08 g, 36.8 mmol) in water (20 mL) at 4° C. After the completion of the addition, the cooling bath was removed and the reaction mixture was stirred at room temperature for 4.5 h. Saturated Na2S2O5 was added slowly to the stirred mixture. The solid was collected through filtration, washed with water, and dried under vacuum overnight to give 9.30 g of 6-amino-5-bromonicotinic acid along with 3,5-dibromo-2-aminopyridine in ˜1:1 ration as a greenish solid; MS (ES) m/z: 217 (M+H+). A mixture of the solid (4.00 g) containing 6-amino-5-bromonicotinic acid, DPPA (6.08 g, 22.1 mmol), triethylamine (2.80 g, 27.7 mmol), benzyl alcohol (3.8 mL, 36.8 mmol), and toluene (50 mL) was heated at 70° C. for 1 h, then 100° C. for 1 h. After concentration, the reaction mixture was purified by flash chromatography (EtOAc/hexane as solvent) to give 1.31 g (26% in 2 steps) of Compound 112b as a yellow solid; 1H NMR (300 MHz, CDCl3) δ7.99 (brs, 1H), 7.91(d, J=2.3 Hz, 1H), 7.39-7.34 (m, 5H), 6.50 (brs, 1H), 5.19 (s, 2H), 4.79 (brs, 2H); MS (ES) m/z: 324 (M+H+). Anal. Calcd. For C13H12BrN3O2.0.1H2O : C, 48.20; H, 3.80; N, 12.97. Found: C, 48.40; H, 3.90; N, 12.64.

1. additionAfter the completion of the addition
2. customthe cooling bath was removed
3. additionSaturated Na2S2O5 was added slowly to the stirred mixture
4. filtrationThe solid was collected through filtration
5. washwashed with water
6. customdried under vacuum overnight

ORD-Eintrag

ord-e3cb16bce429449f9b444337fe57afc8

Quelldatensatz

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06710048B2