Hydrochloric Acid → 1-Chloro-4-[2-(2-methoxy-pyridin-4-yl)-ethyl]-isoquinoline

HRID 49224Notes

Reaction equation

HRID 49224 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][CH2:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14](=O)[NH:13][CH:12]=2)[CH:6]=[CH:5][N:4]=1.P(Cl)(Cl)([Cl:24])=O.Cl.O.N>C(#N)C.O1CCOCC1.CCOC(C)=O>[Cl:24][C:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11]([CH2:10][CH2:9][C:7]2[CH:6]=[CH:5][N:4]=[C:3]([O:2][CH3:1])[CH:8]=2)=[CH:12][N:13]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 12896473Azane;hydrateHCID 20636410HCID 20636410, compound

Product 1

HCID 179484481-Chloro-4-[2-(2-methoxy-pyridin-4-yl)-ethyl]-isoquinoline

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

Under a N2 atmosphere, 160 mg (0.57 mmol) of 4-[2-(2-methoxy-pyridin-4-yl)-ethyl]-2H-isoquinolin-1-one in 3.7 ml of acetonitrile are mixed with 131 μl (1.43 mmol) of phosphorus oxychloride and 0.28 ml of 4 N HCl in dioxane and stirred for 7 h at 65° C. After cooling to RT, water/NH3 conc. 10:1 and EtOAc are added, the water phase is separated and extraction effected twice with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated by evaporation to form 1-chloro-4-[2-(2-methoxy-pyridin-4-yl)-ethyl]-isoquinoline; 1H NMR (DMSO-d6) δ8.30 (d, 1H), 8.27 (d, 1H), 8.13 (s, 1H), 8.03 (d, 1H), 7.94 (t, 1H), 7.85 (t, 1H), 6.90 (d, 1H), 6.73 (s, 1H), 3.80 (s, H3C), 3.32 (t, H2C), 2.95 (t, H2C).

Workup

  1. temperatureAfter cooling to RT
  2. customthe water phase is separated
  3. extractionextraction
  4. washThe organic phases are washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-9dcbf5e6e4504620b5ead4373155e48a
Source dataset
uspto-grants-2004_03
Patent number
US06706731B2

Reaction notes

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