Trifluoroacetic acid → HCID 178496062, compound

HRID 253251Notes

Reaction equation

HRID 253251 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:17]2[C:18]([CH3:23])=[N:19][NH:20][C:21]=2[NH2:22])[CH:9]=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][O:15][CH3:16].[Cl:24][C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][C:32]=1[OH:33])[CH:28]=O.FC(F)(F)C(O)=O>CO>[ClH:24].[Cl:24][C:25]1[CH:26]=[C:27]([C:28]2[C:9]3[CH:10]=[C:11]([O:12][CH2:13][CH2:14][O:15][CH3:16])[C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:7][C:8]=3[C:17]3[C:18]([CH3:23])=[N:19][NH:20][C:21]=3[N:22]=2)[CH:30]=[CH:31][C:32]=1[OH:33]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 170223-Chloro-4-hydroxybenzaldehydeHCID 178496107HCID 178496107, compound

Product 1

HCID 178496062HCID 178496062, compoundYield 47.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-(3,4-bis{[2-(methyloxy)ethyl]oxy}phenyl)-3-methyl-1H-pyrazol-5-amine (114 mg, 0.36 mmol), 3-chloro-4-hydroxybenzaldehyde (117 mg, 0.75 mmol) and trifluoroacetic acid (3 mL) was heated at 70° C. for 18 hours. Then the reaction mixture was concentrated, dissolved in 10 mL of N,N-dimethylformamide and purified by preparatory HPLC (Shimadzu LC-8A HPLC, Waters Xterra C18 30 mm×100 mm column, acetonitrile-water-trifluoroacetic eluent). After concentration then lyophillization of the pure fractions a yellow powder was obtained. It was dissolved in 4 mL of 1:1 methanol: 4M hydrogen chloride in dioxane, and evaporated to dryness (repeated three times) to give 2-chloro-4-(1-methyl-7,8-bis{[2-(methyloxy)ethyl]oxy}-3H-pyrazolo[3,4-c]isoquinolin-5-yl)phenol hydrochloride salt (84 mg, 0.17 mmol, 47% yield) 1H NMR (400 MHz, d6-DMSO): 10.65 (b, 1H), 7.68-7.67 (b, 2H), 7.53-7.48 (m, 2H), 7.16-7.14 (d, 1H), 4.45-4.43 (m, 2H), 4.09-4.07 (m, 2H), 3.80-3.78 (m, 2H), 3.68-3.66 (m, 2H), 3.36 (s, 3H), 3.30 (s, 3H), 2.81 (s, 3H); MS (EI) for C23H24ClN3O5: 458 (MH+).

Workup

  1. concentrationThen the reaction mixture was concentrated
  2. dissolutiondissolved in 10 mL of N,N-dimethylformamide
  3. custompurified by preparatory HPLC (Shimadzu LC-8A HPLC, Waters Xterra C18 30 mm×100 mm column, acetonitrile-water-trifluoroacetic eluent)
  4. concentrationAfter concentration
  5. customlyophillization of the pure fractions a yellow powder was obtained
  6. custom4M hydrogen chloride in dioxane, and evaporated to dryness (repeated three times)

Sources & evidence

ORD record
ord-83700b6e03a9487f9df0f782d8d0efd2
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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