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

HRID 1241453Notes

Reaction equation

HRID 1241453 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 1A) is mixed 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, and the residue is added to 2 l of water and extracted three times with 1 l of ethyl acetate each time. The combined organic phases are dried with magnesium sulfate and concentrated in a rotary evaporator. Chromatography is carried out on 2.5 kg of silica gel, eluting with a toluene/toluene-ethyl acetate=4:1 gradient. Yield: 91.6 g (49.9% of theory over two stages).

Workup

  1. customThe solvent is then evaporated in vacuo
  2. additionthe residue is added to 2 l of water
  3. extractionextracted three times with 1 l of ethyl acetate each time
  4. dry with materialThe combined organic phases are dried with magnesium sulfate
  5. concentrationconcentrated in a rotary evaporator
  6. washeluting with a toluene/toluene-ethyl acetate=4:1 gradient

Sources & evidence

ORD record
ord-2c157b0917094926aff0ab7cecba33c3
Source dataset
uspto-grants-2006_10
Patent number
US07115599B2

Reaction notes

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