Trifluoroacetic acid → 3-Ethoxycarbonyl-1-(2-fluorbenzyl)-1H-pyrazolo-(3,4,5)-pyridin

Reaction equation

[NH2:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[F:14])[N:5]=[C:4]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:3]=1.CN([C:23]([CH:25]=[CH2:26])=O)C.FC(F)(F)C(O)=O>>[F:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[CH2:7][N:6]1[C:2]2=[N:1][CH:23]=[CH:25][CH:26]=[C:3]2[C:4]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:5]1

Participants

Reactant 3

HCID 6422Trifluoroacetic acid

HCID 17587N,N-Dimethylacrylamide

HCID 11391384ethyl 5-amino-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate

Product 1

HCID 111623453-Ethoxycarbonyl-1-(2-fluorbenzyl)-1H-pyrazolo-(3,4,5)-pyridin

Procedure

The solution obtained from 3A) is treated with 61.25 ml (60.77 g, 0.613 mol) of dimethylaminoacrolein and 56.28 ml (83.88 g, 0.736 mol) of trifluoroacetic acid and boiled under argon for 3 days. The solvent is then evaporated in vacuo, the residue is added to 2 l of water and the mixture is extracted three times with 1 l of ethyl acetate each time. The combined organic phases are dried using magnesium sulphate and concentrated in a rotary evaporator. The residue is chromatographed on 2.5 g of silica gel and eluted with a toluene/toluene-ethyl acetate=4:1 gradient. Yield: 91.6 g (49.9% of theory over two steps).