Ammonia → 3-(3,5-dimethyl-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-6,8-dimethoxyisoquinolin-1(2H)-one

HRID 336669Notes

Reaction equation

HRID 336669 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[O:13][C:14](=O)[C:15]3[C:20]([CH:21]=2)=[CH:19][C:18]([O:22][CH3:23])=[CH:17][C:16]=3[O:24][CH3:25])=[CH:7][C:6]=1[CH3:27].[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.CC[N:37](CC)CC.CC1OC(=O)C2C(C=1C1C=CC=CC=1OCCN1CCN(C)CC1)=C(C)C(OC)=CC=2OC.N>CS(C)=O.O>[CH3:11][C:10]1[CH:9]=[C:8]([C:12]2[NH:37][C:14](=[O:13])[C:15]3[C:20]([CH:21]=2)=[CH:19][C:18]([O:22][CH3:23])=[CH:17][C:16]=3[O:24][CH3:25])[CH:7]=[C:6]([CH3:27])[C:5]=1[O:4][CH2:3][CH2:2][N:32]1[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 666614363-[4-(2-Chloro-ethoxy)-3,5-dimethyl-phenyl]-6,8-dimethoxy-isochromen-1-oneHCID 86661270HCID 86661270, compound

Product 1

HCID 249578633-(3,5-dimethyl-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-6,8-dimethoxyisoquinolin-1(2H)-one

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

The compound 3-[4-(2-chloro-ethoxy)-3,5-dimethyl-phenyl]-6,8-dimethoxy-isochromen-1-one (298 mg, 0.767 mmol) was dissolved in DMSO (5 mL) and N-methyl piperazine (388 mg, 3.83 mmol) and Et3N (392 mg, 3.83 mmol) were added. The reaction mixture was heated at 110° C. for 16 h before being cooled to room temperature. Water was added and the mixture was extracted with ethyl acetate. The solvent was evaporated in vacuo to leave a residue which was purified by column chromatography. The yield was 60 mg (17%). The compound 3-[3,5-dimethyl-4-(2-(4-methyl piperazin-1-yl-ethoxy)-phenyl]-6,8-dimethoxy-isochromen-1-one (60 mg, 0.13 mmol) and NH3 (2.0 M solution in ethanol, 20 mL) were mixed in a steel bomb and heated at 130° C. for 16 h. The solvent was removed and the crude compound was purified by column chromatography. The compound was then converted to the hydrochloride salt of 3-(3,5-dimethyl-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-6,8-dimethoxyisoquinolin-1(2H)-one (40 mg, 62%), an off-white solid. Selected data: MS (ES) m/z: 452.1; MP 195-198° C. (HCl salt).

Workup

  1. temperaturebefore being cooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. customThe solvent was evaporated in vacuo
  4. customto leave a residue which
  5. customwas purified by column chromatography
  6. temperatureheated at 130° C. for 16 h
  7. customThe solvent was removed
  8. customthe crude compound was purified by column chromatography

Sources & evidence

ORD record
ord-b3b73ba69c8042808dabe9624699afbb
Source dataset
uspto-grants-2014_11
Patent number
US08889698B2

Reaction notes

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