Phosphorus oxychloride → HCID 22502633, compound

HRID 1251259Notes

Reaction equation

HRID 1251259 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 resulting mixture 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-57407f18fea14f63bf94e4e3e5165c41
Source dataset
uspto-grants-2002_01
Patent number
US06340759B1

Reaction notes

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