Phosphorus oxychloride → HCID 86683276, compound

HRID 1852269Notes

Reaction equation

HRID 1852269 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=O)[NH:8][CH:7]=[C:6]2[N:14]1[CH:18]=[CH:17][CH:16]=[N:15]1.P(Cl)(Cl)([Cl:21])=O>>[Cl:21][C:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2)[C:6]([N:14]2[CH:18]=[CH:17][CH:16]=[N:15]2)=[CH:7][N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 70979009HCID 70979009, compound

Product 1

HCID 86683276HCID 86683276, compoundYield 6%

Conditions

Temperature
100 °C

Procedure

6-methoxy-4-(1H-pyrazol-1-yl) isoquinolin-1(2H)-one (0.25 g, 1.036 mmol) was taken in phosphorous oxychloride (5 mL) and stirred for 1 h at 100° C. The volatiles were evaporated and the crude was poured into ice. The pH was adjusted to 9.0, extracted with ethyl acetate and washed with brine solution. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure. The crude product was purified by silica gel chromatrography using 10% Ethyl acetate in Pet-ether to get 1-chloro-6-methoxy-4-(1H-pyrazol-1-yl)isoquinoline (0.019 g, 0.062 mmol, 6.00% yield) as solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.77-8.84 (m, 2H) 8.74-8.84 (m, 1H) 8.52-8.58 (m, 2H) 8.52-8.57 (m, 1H) 8.28-8.34 (m, 1H) 8.27-8.34 (m, 2H) 7.90-7.96 (m, 1H) 7.77-7.83 (m, 1H) 7.46-7.52 (m, 1H) 7.32-7.38 (m, 1H) 6.58-6.66 (m, 1H) 3.96 (s, 3H). MS: MS m/z 260.10 (M++1).

Workup

  1. customThe volatiles were evaporated
  2. additionthe crude was poured into ice
  3. extractionextracted with ethyl acetate
  4. washwashed with brine solution
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by silica gel chromatrography

Sources & evidence

ORD record
ord-e1d4db02f0ed48be990418c7d9bde91f
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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