Sodium Carbonate → HCID 22503364, compound

HRID 1006986Notes

Reaction equation

HRID 1006986 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](OB(O)O)=[CH:11][C:10]=1[F:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:21]1[N:22]=[C:23]([N:31]2[CH2:36][CH2:35][N:34]([CH2:37][CH3:38])[CH2:33][CH2:32]2)[C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:37]([N:34]1[CH2:33][CH2:32][N:31]([C:23]2[C:24]3[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:30]=[C:21]([C:12]3[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[C:10]([F:19])[CH:11]=3)[N:22]=2)[CH2:36][CH2:35]1)[CH3:38]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 225024471-(1-Ethylpiperazin-4-yl)-3-bromoisoquinolineHCID 22503033HCID 22503033, compound3×

Product 1

HCID 22503364HCID 22503364, compoundYield 96.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

4-Benzyloxy-3-fluorophenylboric acid (1.97 g) and 3-bromo-1-(4-ethylpiperazin-1-yl)isoquinoline (2.57 g) were heated under reflux in the presence of tetrakistriphenylphosphinepalladium(0) (0.09 g) in toluene (250 ml) and a 10% aqueous solution of sodium carbonate (150 ml) in nitrogen atmosphere for 2 hr. 4-Benzyloxy-3-fluorophenylboric acid (0.99 g) was additionally added thereto, and the mixture was heated under reflux for 30 min. 4-Benzyloxy-3-fluorophenylboric acid (1.43 g) was again added thereto, and the mixture was heated under reflux overnight. The organic layer was separated and extracted with 2N hydrochloric acid twice, and the resulting aqueous layer was washed with ethyl acetate. Then, it was adjusted to pH 10 by a 8N aqueous solution of sodium hydroxide, extracted with ethyl acetate, washed with a 10% aqueous solution of sodium carbonate and brine, and dried over magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (chloroform/methanol system), to give obtain 1-(4-ethylpiperazin-1-yl)-3-(4-benzyloxy-3-fluorophenyl)isoquinoline (3.19 g) as a brown viscous oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 30 min
  3. temperaturethe mixture was heated
  4. temperatureunder reflux overnight
  5. customThe organic layer was separated
  6. extractionextracted with 2N hydrochloric acid twice
  7. washthe resulting aqueous layer was washed with ethyl acetate
  8. extractionextracted with ethyl acetate
  9. washwashed with a 10% aqueous solution of sodium carbonate and brine
  10. dry with materialdried over magnesium sulfate
  11. customThe solvent was evaporated
  12. customthe resulting residue was purified by silica gel column chromatography (chloroform/methanol system)
  13. customto give

Sources & evidence

ORD record
ord-e3307112adfa40e7afb7aaa635acc866
Source dataset
uspto-grants-2004_09
Patent number
US06790844B2

Reaction notes

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