Sodium Carbonate → 4-(7-chloro-1H-indazol-5-yl)-isoquinoline

HRID 1526746Notes

Reaction equation

HRID 1526746 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](B(O)O)=[CH:3][N:2]=1.Br[C:15]1[CH:16]=[C:17]2[C:21](=[C:22]([Cl:24])[CH:23]=1)[NH:20][N:19]=[CH:18]2.C(=O)([O-])[O-].[Na+].[Na+]>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.C(COC)OC>[Cl:24][C:22]1[CH:23]=[C:15]([C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=[N:2][CH:3]=2)[CH:16]=[C:17]2[C:21]=1[NH:20][N:19]=[CH:18]2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 3761204Isoquinoline-4-boronic acidHCID 211021945-Bromo-7-chloro-1H-indazole

Product 1

HCID 689979964-(7-chloro-1H-indazol-5-yl)-isoquinolineYield 72.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of isoquinolin-4-ylboronic acid (1.00 g, 5.78 mmol), 5-bromo-7-chloro-1H-indazole (892 mg, 3.85 mmol), 2.0 M sodium carbonate (3.85 mL, 7.71 mmol) and dimethoxyethane was degassed with argon. Tetrakis(triphenylphosphine)palladium(0) (233 mg, 0.193 mmol) was added, the mixture degassed again with argon, then heated to 85° C. for 24 hours. The reaction was cooled and partitioned between ethyl acetate and water, the organic layer washed with and dried with sodium sulfate. The solvent was removed under vacuum and the residue purified by column chromatography (9/1 to 6/4 hexanes/ethyl acetate gradient) to give 4-(7-chloro-1H-indazol-5-yl)-isoquinoline (777 mg, 72%): 1H NMR (300 MHz, CDCl3) δ 10.52 (s, 1H) 9.31 (s, 1H), 8.53 (s, 1H), 8.22 (s, 1H), 8.09 (dd, J=7.4, 1.62 Hz, 1H), 7.28 (dd, J=7.4, 1.2 Hz, 1H), 7.87 (d, J=9.0 Hz, 1H), 7.81 (d, J=1.2 Hz, 1H), 7.72-7.64 (m, 2H), 7.57 (d, J=1.3 Hz, 1H).

Workup

  1. customwas degassed with argon
  2. customthe mixture degassed again with argon
  3. temperatureThe reaction was cooled
  4. custompartitioned between ethyl acetate and water
  5. washthe organic layer washed with and
  6. dry with materialdried with sodium sulfate
  7. customThe solvent was removed under vacuum
  8. customthe residue purified by column chromatography (9/1 to 6/4 hexanes/ethyl acetate gradient)

Sources & evidence

ORD record
ord-b233d54b371d42879c60d199f8080a30
Source dataset
uspto-grants-2015_07
Patent number
US09085531B2

Reaction notes

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