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

HRID 2120567Notes

Reaction equation

HRID 2120567 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

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 17587N,N-DimethylacrylamideHCID 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).

Workup

  1. customThe solvent is then evaporated in vacuo
  2. additionthe residue is added to 2 l of water
  3. extractionthe mixture is extracted three times with 1 l of ethyl acetate each time
  4. customThe combined organic phases are dried
  5. concentrationconcentrated in a rotary evaporator
  6. customThe residue is chromatographed on 2.5 g of silica gel
  7. washeluted with a toluene/toluene-ethyl acetate=4:1 gradient

Sources & evidence

ORD record
ord-77311ec7313649e19b71dadc8421b82e
Source dataset
uspto-grants-2004_02
Patent number
US06693102B2

Reaction notes

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