Sodium Carbonate → HCID 44176973, compound

HRID 2090159Notes

Reaction equation

HRID 2090159 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][CH:13]=[CH:12]3)[CH:5]=[N:4][CH:3]=1.[F:18][C:19]1[CH:24]=[C:23](B(O)O)[CH:22]=[CH:21][N:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.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>[F:18][C:19]1[CH:24]=[C:23]([C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:10]=[C:11]4[C:15](=[CH:16][CH:17]=3)[NH:14][CH:13]=[CH:12]4)[CH:5]=[N:4][CH:3]=2)[CH:22]=[CH:21][N:20]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 86652754HCID 86652754, compound

Product 1

HCID 44176973HCID 44176973, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

A mixture of N-(6-chloro-pyrazin-2-yl)-1H-indol-5-amine (0.05 g, 0.205 mmol), 2-fluoropyridine-4-boronic acid (0.057 g, 0.4 mmol), sodium carbonate (0.112 g, 1.025 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.012 g, 0.01 mmol) in DME:water (3:2, 3 mL) was heated at reflux for 20 h. The reaction mixture was concentrated under reduced pressure and the residue obtained was extracted with dichloromethane. The organic layer was washed with water, brine, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography (5% methanol in CH2Cl2 as eluent) to yield the title compound (0.015 g, 24%) as a yellow solid. 1H NMR (CD3OD) δ 8.47 (s, 1H), 8.35-8.33 (d, J=5.29 Hz, 1H), 8.16 (s, 1H), 8.01-8.00 (d, J=5.13 Hz, 1H), 7.94 (s, 1H), 7.78 (s, 1H), 7.45-7.43 (d, J=8.64 Hz, 1H), 7.35-7.33 (dd, J=10.33, 1.72 Hz, 1H), 7.29 (d, J=2.95 Hz, 1H), 6.48-6.47 (d, J=2.58 Hz, 1H); MS (API-ES/Positive); m/z: 306 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 20 h
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customthe residue obtained
  5. extractionwas extracted with dichloromethane
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography (5% methanol in CH2Cl2 as eluent)

Sources & evidence

ORD record
ord-a3fa7d11ec86449b97da125d80f78488
Source dataset
uspto-grants-2013_05
Patent number
US08436171B2

Reaction notes

Loading…