Phosphorus oxychloride → 1-Chloro-3-(5-isopropoxypyridin-2-yl)-6-methoxyisoquinoline

HRID 1852064Notes

Reaction equation

HRID 1852064 reaction equation
[CH:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]2[N:12]=[C:13](O)[C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([O:21][CH3:22])=[CH:16][CH:15]=3)=[N:9][CH:10]=1)([CH3:3])[CH3:2].O=P(Cl)(Cl)[Cl:26]>>[Cl:26][C:13]1[C:14]2[C:19](=[CH:18][C:17]([O:21][CH3:22])=[CH:16][CH:15]=2)[CH:20]=[C:11]([C:8]2[CH:7]=[CH:6][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[CH:10][N:9]=2)[N:12]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178487736HCID 178487736, compound

Product 1

HCID 866831731-Chloro-3-(5-isopropoxypyridin-2-yl)-6-methoxyisoquinoline

Procedure

A solution of 3-(5-isopropoxypyridin-2-yl)-6-methoxyisoquinolin-1-ol (4 g, 12.89 mmol) in POCl3 (20 mL) was refluxed for 2 hs. After concentration, the residue was taken into the mixture of DCM and 4N NaOH solution. The organic phase was collected and dried over sodium sulfate, filtered, then concentrated under vacuum. The crude material was purified by silica gel chromatography using CH2Cl2 as eluent to give 3.4 g of the desired product 1-chloro-3-(5-isopropoxypyridin-2-yl)-6-methoxyisoquinoline as a solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.49 (s, 1H), 8.39 (d, J=8.8 Hz, 1H), 8.33 (d, J=2.5 Hz, 1H), 8.19 (d, J=9.1 Hz, 1H), 7.29 (dd, J=8.8, 3.0 Hz, 1H), 7.23 (dd, J=6.8, 2.5 Hz, 1H), 7.16 (d, J=2.3 Hz, 1H), 4.65 (spt, J=6.0 Hz, 1H), 3.94 (s, 3H), 1.38 (d, J=6.3 Hz, 6H).

Workup

  1. concentrationAfter concentration
  2. additionthe residue was taken into the mixture of DCM and 4N NaOH solution
  3. customThe organic phase was collected
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-d773b4d208684bdebd94da82bcdb9de0
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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