Triethylamine → HCID 86673064, compound

HRID 1853293Notes

Reaction equation

HRID 1853293 reaction equation
[C:1]([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][C:13]([C:17]#[C:18][CH2:19]O)=[CH:14][CH:15]=2)[O:10][C:9]([C:21]2[N:22]=[CH:23][C:24]3[C:29]([CH:30]=2)=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:8]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CS(Cl)(=O)=O.[Cl-].[NH4+].C(=O)([O-])[O-].[K+].[K+].[CH3:51][N:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1>ClCCl>[C:1]([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][C:13]([C:17]#[C:18][CH2:19][N:55]3[CH2:56][CH2:57][N:52]([CH3:51])[CH2:53][CH2:54]3)=[CH:14][CH:15]=2)[O:10][C:9]([C:21]2[N:22]=[CH:23][C:24]3[C:29]([CH:30]=2)=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:8]1)([CH3:3])([CH3:4])[CH3:2]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 531671-MethylpiperazineHCID 86673061HCID 86673061, compound

Product 1

HCID 86673064HCID 86673064, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a cold solution of 7-(3-Hydroxy-prop-1-ynyl)-2-isoquinolin-3-yl-chromen-4-one O-tert-butyl oxime (example 54A) (230 mg, 0.577 mmol) and triethylamine (0.18 ml, 1.27 mmol) in dichloromethane (3 ml) was added dropwise methanesulfonyl chloride (90 μl, 1.15 mmol). The reaction mixture was stirred for 4 hours at 0° C. and poured onto a saturated solution of ammonium chloride. The product was extracted with dichloromethane, washed with brine, dried over sodium sulfate and concentrated to dryness. The residue methansulfonic ester was dissolved in acetone (3 ml) and treated with potassium carbonate (239 mg, 1.73 mmol) and methyl piperazine (87 mg, 0.866 mmol) and the mixture was stirred at 25° C. for 20 hours. The mixture was poured onto water and extracted with ethyl acetate, washed with water, brine, dried over sodium sulfate and absorbed over silica gel for purification by flash chromatography (ethyl acetate/methanol 90/10 then ethyl acetate/7N ammoniac in methanol: 90/10) to yield 2-isoquinolin-3-yl-7-[3-(4-methyl-piperazin-1-yl)-prop-1-ynyl]-chromen-4-one O-tert-butyl oxime (49 mg, 18%) as a brown solid.

Workup

  1. extractionThe product was extracted with dichloromethane
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to dryness
  5. dissolutionThe residue methansulfonic ester was dissolved in acetone (3 ml)
  6. stirringthe mixture was stirred at 25° C. for 20 hours
  7. additionThe mixture was poured onto water
  8. extractionextracted with ethyl acetate
  9. washwashed with water, brine
  10. dry with materialdried over sodium sulfate
  11. customabsorbed over silica gel for purification by flash chromatography (ethyl acetate/methanol 90/10

Sources & evidence

ORD record
ord-5d49cdb4ede94c8383123b0dc9a53c39
Source dataset
uspto-grants-2015_02
Patent number
US08962627B2

Reaction notes

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