Potassium Carbonate → 1-Chloro-7-(1H-indol-5-yl)-isoquinoline

HRID 63245

Reaction equation

HRID 63245 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[Cl:12])=[CH:4][CH:3]=1.[NH:13]1[C:21]2[C:16](=[CH:17][C:18](B(O)O)=[CH:19][CH:20]=2)[CH:15]=[CH:14]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:12][C:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([C:18]3[CH:17]=[C:16]4[C:21](=[CH:20][CH:19]=3)[NH:13][CH:14]=[CH:15]4)[CH:11]=2)[CH:6]=[CH:7][N:8]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343615-Indolylboronic acidHCID 65020247-Bromo-1-Chloroisoquinoline

Product 1

HCID 575168401-Chloro-7-(1H-indol-5-yl)-isoquinolineYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 7-bromo-1-chloroisoquinoline (0.50 g, 2.1 mmol), 5-indoleboronic acid (0.40 g, 2.5 mmol), tetrakis(triphenylphosphene)palladium (0.035 g, 0.08 mmol), potassium carbonate (2.1 mL, 2 M, 4.1 mmol), N,N-dimethylformamide (11 mL) was stirred while purging the headspace with argon for 30 min. The mixture was then brought to reflux for 16 h before being allowed to cool to RT. The mixture was filtered through a bed of silica gel, diluted with water (50 mL), and extracted with ethyl acetate (50 mL). The organic layer was separated and washed with NaOH (2×20 mL, 10% aq.), water (5×30 mL, until refractive changes were no longer seen at the organic-aqueous interface), and ammonium chloride (20 mL, sat.). The organic layer was then adsorbed onto silica gel and flash-chromatographed (ethyl acetate/hexanes) to afford 0.14 g (25%) of a yellow solid. MS (ESI): calculated for C17H11ClN2, 278.1. found 301.0 [M+Na]+. 1H NMR (300 MHz, DMSO-d6) δ 6.56-6.58 (m, 1H), 7.44 (t, J=2.77 Hz, 1H), 7.57-7.59 (m, 2H), 7.93 (m, 1H), 8.04 (s, 1H), 8.13-8.20 (m, 1H), 8.27-8.31 (m, 2H), 8.43 (m, 1H), 11.25 (brs, 1H).

Workup

  1. customwhile purging the headspace with argon for 30 min
  2. temperatureto reflux for 16 h
  3. filtrationThe mixture was filtered through a bed of silica gel
  4. additiondiluted with water (50 mL)
  5. extractionextracted with ethyl acetate (50 mL)
  6. customThe organic layer was separated
  7. washwashed with NaOH (2×20 mL, 10% aq.), water (5×30 mL
  8. customflash-chromatographed (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-01d251adb4af45f19b68e80ee76c7def
Source dataset
uspto-grants-2016_09
Patent number
US09447049B2

Linked notes

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