Trifluoroacetic acid → HCID 178496095, compound

HRID 253258Notes

Reaction equation

HRID 253258 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])[C:8]=2[O:18][CH3:19])=[C:5]([NH2:20])[NH:4][N:3]=1.[Cl:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:29]=1[OH:30])[CH:25]=O.FC(F)(F)C(O)=O>CO>[ClH:21].[Cl:21][C:22]1[CH:23]=[C:24]([C:25]2[C:12]3[CH:11]=[CH:10][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[C:8]([O:18][CH3:19])[C:7]=3[C:6]3[C:2]([CH3:1])=[N:3][NH:4][C:5]=3[N:20]=2)[CH:27]=[CH:28][C:29]=1[OH:30]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 170223-Chloro-4-hydroxybenzaldehydeHCID 178496120HCID 178496120, compound

Product 1

HCID 178496095HCID 178496095, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-methyl-4-(2-(methyloxy)-3-{[2-(methyloxy)ethyl]oxy}phenyl)-1H-pyrazol-5-amine (115 mg, 0.42 mmol), 3-chloro-4-hydroxybenzaldehyde (100 mg, 0.64 mmol) and trifluoroacetic acid (3 mL) was heated at 70° C. for 18 hours. 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 acid eluent). After concentration and lyophillization of the pure fractions a yellow powder was obtained. The solid was dissolved in 4 mL of 1:1 methanol: 4M hydrogen chloride in dioxane, and evaporated to dryness (repeated three times) yielded 2-chloro-4-(1-methyl-9-(methyloxy)-8-{[2-(methyloxy)ethyl]oxy}-3H-pyrazolo[3,4-c]isoquinolin-5-yl)phenol hydrochloride salt (76 mg, 0.17 mmol, 40% yield) 1H NMR (400 MHz, d6-DMSO): 10.82 (b, 1H), 7.80-7.78 (d, 1H), 7.65 (s, 1H), 746-7.44 (m, 2H), 7.18-7.16 (d, 1H), 4.37-4.35 (m, 2H), 3.94 (s, 3H), 3.78-3.76 (m, 2H), 3.36 (s, 3H), 2.83 (s, 3H); MS (EI) for C21H20ClN3O4: 414 (MH+).

Workup

  1. concentrationThe 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 acid eluent)
  4. concentrationAfter concentration and lyophillization of the pure fractions a yellow powder
  5. customwas obtained
  6. custom4M hydrogen chloride in dioxane, and evaporated to dryness (repeated three times)

Sources & evidence

ORD record
ord-14cd62a887e74608babd971fc14b9f86
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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