Dichloromethane → 2-(Trimethylsilyl)ethyl 4-[4-(4-acetylpiperazin-1-yl)phenyl]isoquinoline-6-carboxylate

HRID 1959959Notes

Reaction equation

HRID 1959959 reaction equation
ClCCl.C([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]3[C:32]4[C:27](=[CH:28][CH:29]=[C:30]([C:33]([O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])=[O:34])[CH:31]=4)[CH:26]=[N:25][CH:24]=3)=[CH:19][CH:18]=2)[CH2:13][CH2:12]1)=O)(C)(C)C.F[C:43](F)(F)C(O)=O>N1C=CC=CC=1.C(O)(=O)C>[C:9]([N:11]1[CH2:12][CH2:13][N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]3[C:32]4[C:27](=[CH:28][CH:29]=[C:30]([C:33]([O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:39])[CH3:40])=[O:34])[CH:31]=4)[CH:26]=[N:25][CH:24]=3)=[CH:19][CH:18]=2)[CH2:15][CH2:16]1)(=[O:8])[CH3:43]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 667455782-(Trimethylsilyl)ethyl 4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}isoquinoline-6-carboxylate

Product 1

HCID 667303852-(Trimethylsilyl)ethyl 4-[4-(4-acetylpiperazin-1-yl)phenyl]isoquinoline-6-carboxylateYield 58%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 1049PyridineSolvent

Procedure

Into dichloromethane (5 mL), 2-(trimethylsilyl)ethyl 4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}isoquinoline-6-carboxylate (103 mg, 0.193 mmol) synthesized in Example 16 (16a) was dissolved, to which trifluoroacetic acid (0.5 mL) was added, followed by stirring at room temperature for three hours. After concentration, the resulting mixture was diluted with dichloromethane (20 mL) and neutralized with a saturated aqueous solution of sodium bicarbonate (15 mL). The resulting organic layer was dried over sodium sulfate and filtered. The solvent was distilled off under reduced pressure. The residue thus obtained was dissolved in pyridine (5 mL), to which anhydrous acetic acid (0.5 mL) was added, followed by stirring at room temperature overnight. After concentration, the resulting mixture was diluted with dichloromethane (20 mL) and neutralized with a saturated aqueous solution of sodium bicarbonate (15 mL). The solution thus obtained was extracted with dichloromethane (20 mL), and the resulting organic layer was dried over sodium sulfate and filtered. The solvent was distilled off under reduced pressure and the resulting product was purified by thin layer chromatography (dichloromethane:methanol=97:3) to give the desired title compound (54 mg, yield 58%).

Workup

  1. additionwas added
  2. concentrationAfter concentration
  3. additionthe resulting mixture was diluted with dichloromethane (20 mL)
  4. dry with materialThe resulting organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. distillationThe solvent was distilled off under reduced pressure
  7. customThe residue thus obtained
  8. additionwas added
  9. stirringby stirring at room temperature overnight
  10. concentrationAfter concentration
  11. additionthe resulting mixture was diluted with dichloromethane (20 mL)
  12. customThe solution thus obtained
  13. extractionwas extracted with dichloromethane (20 mL)
  14. dry with materialthe resulting organic layer was dried over sodium sulfate
  15. filtrationfiltered
  16. distillationThe solvent was distilled off under reduced pressure
  17. customthe resulting product was purified by thin layer chromatography (dichloromethane:methanol=97:3)

Sources & evidence

ORD record
ord-3d44a6fc02924ef0a9759a1ce09c2b10
Source dataset
uspto-grants-2013_04
Patent number
US08410273B2

Reaction notes

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