HCID 13911432, compound → HCID 57558054, compound

HRID 1162932Notes

Reaction equation

HRID 1162932 reaction equation
[CH3:1][C:2]1([CH3:10])[O:9][CH2:8][C:5]2([O:7][CH2:6]2)[CH2:4][O:3]1.[NH2:11][C:12]1[CH:21]=[C:20]2[C:15]([CH:16]=[C:17]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]([F:32])([F:31])[F:30])[NH:18][C:19]2=[O:22])=[CH:14][CH:13]=1>C(O)C.[Br-].[Li+]>[OH:7][C:5]1([CH2:6][NH:11][C:12]2[CH:21]=[C:20]3[C:15]([CH:16]=[C:17]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[C:29]([F:32])([F:30])[F:31])[NH:18][C:19]3=[O:22])=[CH:14][CH:13]=2)[CH2:8][O:9][C:2]([CH3:10])([CH3:1])[O:3][CH2:4]1

Participants

5

Reactant 2

HCID 13911432HCID 13911432, compoundHCID 231567387-amino-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

Product 1

HCID 57558054HCID 57558054, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 82050Lithium BromideCatalystHCID 702EthanolSolvent

Procedure

6,6-Dimethyl-1,5,7-trioxaspiro[2.5]octane (292 mg, 2.03 mmol) prepared according to a known method described in publications (EP227338, for example) and the 7-amino-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (154 mg, 0.506 mmol) obtained in step C of Example 1-1 were dissolved in ethanol (4 ml). The obtained mixture was stirred at a room temperature for 4 hours and then stirred under heating to reflux for 18 hours. Thereafter, lithium bromide (0.2 mg, mmol) was added to the reaction solution at a room temperature, and the obtained mixture was then stirred for 3 hours. Thereafter, the reaction solution was concentrated, and water was then added thereto, followed by extraction with ethyl acetate. The extract was washed with water and a saturated saline solution, and was then dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=40:1 to 20:1), so as to obtain 7-[(5-hydroxy-2,2-dimethyl-[1,3]dioxan-5-ylmethyl)amino]-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (163 mg, 72%).

Workup

  1. stirringstirred
  2. temperatureunder heating
  3. temperatureto reflux for 18 hours
  4. stirringthe obtained mixture was then stirred for 3 hours
  5. concentrationThereafter, the reaction solution was concentrated
  6. additionwater was then added
  7. extractionfollowed by extraction with ethyl acetate
  8. washThe extract was washed with water
  9. dry with materiala saturated saline solution, and was then dried over anhydrous sodium sulfate
  10. distillationThe solvent was distilled away under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=40:1 to 20:1)

Sources & evidence

ORD record
ord-cf0ea1451ca34f19952131c3a8a3a400
Source dataset
uspto-grants-2010_10
Patent number
US07820693B2

Reaction notes

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