Phosphorus oxychloride → HCID 22502633, compound

HRID 1007019Notes

Reaction equation

HRID 1007019 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:6]([CH3:11])=[CH:7][CH:8]=[CH:9][CH:10]=1)=O.[C:12]([C:14]1[CH:19]=[CH:18][N:17]=[C:16]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:15]=1)#[N:13].P(Cl)(Cl)([Cl:30])=O.[CH2:33]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)[CH3:34]>>[CH2:33]([N:35]1[CH2:36][CH2:37][N:2]([C:3]2[C:5]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:15]=3)[N:13]=2)[CH2:1][CH2:40]1)[CH3:34].[CH2:33]([N:35]1[CH2:40][CH2:39][N:38]([C:11]2[C:6]3[C:5](=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH:3]=[C:12]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([Cl:30])[CH:15]=3)[N:13]=2)[CH2:37][CH2:36]1)[CH3:34]

Participants

6

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 75111N-methyl-2-toluamideHCID 791961-EthylpiperazineHCID 225035202-(benzyloxy)isonicotinonitrile

Product 2

HCID 22502633HCID 22502633, compoundHCID 22502709HCID 22502709, compound

Conditions

Temperature
100 °C

Procedure

To 3-(2-benzyloxypyridin-4-yl)isoquinolin-1-one (2.84 g) obtained by reacting N-methyl-o-toluamide (3.00 g) and 4-cyano-2-benzyloxypyridine (4.20 g) according to the method of Example 10-1 was added phosphorus oxychloride (37.7 g), and the resultingmixture was heated at 100° C. for 2 hr. The reaction solution was evaporated, and to the resulting residue were added ethyl acetate and purified water. The ethyl acetate layer was washed with water and brine, and dried over magnesium sulfate. The solvent was evaporated, and the resulting 1-chloro-3-(2-benzyloxypyridin-4-yl)isoquinoline was reacted as it was with N-ethylpiperazine (20 ml) at 120° C. for 8 hr. The reaction solution was evaporated, and to the resulting residue were added ethyl acetate and purified water. The ethyl acetate layer was washed with water and brine, and dried over magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (methylene chloride/methanol system), to give 1-(4-ethylpiperazin-1-yl)-3-(2-benzyloxypyridin-4-yl)isoquinoline (0.21 g) and 1-(4-ethylpiperazin-1-yl)-3-(2-chloropyridin-4-yl)isoquinoline (0.32 g), as pale yellow oils.

Workup

  1. customThe reaction solution was evaporated
  2. additionto the resulting residue were added ethyl acetate
  3. custompurified water
  4. washThe ethyl acetate layer was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. customThe solvent was evaporated
  7. customthe resulting 1-chloro-3-(2-benzyloxypyridin-4-yl)isoquinoline was reacted as it
  8. customThe reaction solution was evaporated
  9. additionto the resulting residue were added ethyl acetate
  10. custompurified water
  11. washThe ethyl acetate layer was washed with water and brine
  12. dry with materialdried over magnesium sulfate
  13. customThe solvent was evaporated
  14. customthe resulting residue was purified by silica gel column chromatography (methylene chloride/methanol system)

Sources & evidence

ORD record
ord-88830bfe074542658d3d9edb0a75cb07
Source dataset
uspto-grants-2004_09
Patent number
US06790844B2

Reaction notes

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