Sodium Carbonate → HCID 22503215, compound

HRID 1006988Notes

Reaction equation

HRID 1006988 reaction equation
[CH2:1]([O:8][C:9]1[C:14]([F:15])=[CH:13][C:12](OB(O)O)=[CH:11][C:10]=1[F:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:22]1[N:23]=[C:24]([N:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH3:39])[CH2:34][CH2:33]2)[C:25]2[C:30]([CH:31]=1)=[CH:29][CH:28]=[CH:27][CH:26]=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>[CH2:38]([N:35]1[CH2:34][CH2:33][N:32]([C:24]2[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:31]=[C:22]([C:12]3[CH:13]=[C:14]([F:15])[C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[C:10]([F:20])[CH:11]=3)[N:23]=2)[CH2:37][CH2:36]1)[CH3:39]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 225024471-(1-Ethylpiperazin-4-yl)-3-bromoisoquinolineHCID 22502804HCID 22502804, compound3×

Product 1

HCID 22503215HCID 22503215, compoundYield 199.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

4-Benzyloxy-3,5-difluorophenylboric acid (1.97 g) and 3-bromo-1-(4-ethylpiperazin-1-yl)isoquinoline (5.20 g) were heated under reflux in the presence of tetrakistriphenylphosphinepalladium(0) (0.50 g) in toluene (250 ml) and a 10% aqueous solution of sodium carbonate (150 ml) in nitrogen atmosphere for 1 hr. 4-Benzyloxy-3,5-difluorophenylboric acid (1.15 g) was additionally added thereto, and the mixture was heated under reflux for 1 hr. 4-Benzyloxy-3,5-difluorophenylboric acid (1.15 g) was additionally added to the resulting mixture, and then heated under reflux overnight. The organic layer was separated and extracted with 2N hydrochloric acid twice. The resulting aqueous layer was washed with ethyl acetate, 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 1-(4-ethylpiperazin-1-yl)-3-(4-benzyloxy-3,5-difluorophenyl)isoquinoline (6.44 g) as a brown viscous oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 1 hr
  3. temperatureheated
  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)

Sources & evidence

ORD record
ord-5f974d8f8a284ca2b6732a9434754147
Source dataset
uspto-grants-2004_09
Patent number
US06790844B2

Reaction notes

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