Trifluoroacetic acid → HCID 178496139, compound

HRID 253318Notes

Reaction equation

HRID 253318 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([O:20][CH2:21][CH2:22][O:23][CH3:24])[C:5]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[C:6]([C:8]2[C:9]([CH3:14])=[N:10][NH:11][C:12]=2[NH2:13])[CH:7]=1.[Cl:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=1[OH:34])[CH:29]=O.FC(F)(F)C(O)=O>CO>[ClH:25].[Cl:25][C:26]1[CH:27]=[C:28]([C:29]2[C:7]3[C:2]([F:1])=[CH:3][C:4]([O:20][CH2:21][CH2:22][O:23][CH3:24])=[C:5]([O:15][CH2:16][CH2:17][O:18][CH3:19])[C:6]=3[C:8]3[C:9]([CH3:14])=[N:10][NH:11][C:12]=3[N:13]=2)[CH:31]=[CH:32][C:33]=1[OH:34]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 170223-Chloro-4-hydroxybenzaldehydeHCID 178496140HCID 178496140, compound

Product 1

HCID 178496139HCID 178496139, compoundYield 33.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-(5-fluoro-2,3-bis{[2-(methyloxy)ethyl]oxy}phenyl)-3-methyl-1H-pyrazol-5-amine 0.153 mg, 0.45 mmol), 3-chloro-4-hydroxybenzaldehyde (141 mg, 0.9 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-(6-fluoro-1-methyl-8,9-bis{[2-(methyloxy)ethyl]oxy}-3H-pyrazolo[3,4-c]isoquinolin-5-yl)phenol hydrochloric acid salt (77 mg, 0.15 mmol, 33% yield), 1H NMR (400 MHz, d6-DMSO): 10.48 (b, 1H), 7.48 (s, 1H), 7.32-7.28 (m, 2H), 7.05-7.03 (d, 1H), 4.35-4.33 (m, 2H), 4.25-4.21 (m, 2H), 3.77-3.75 (m, 2H), 3.69-3.66 (m, 2H), 3.35 (s, 3H), 3.22 (s, 3H), 2.80 (s, 3H); MS (EI) for C23H23ClFN3O5: 476 (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-511cf02527304904b17a9d8f5d005f22
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

Loading…