2-Bromo-5-chloropyridine → HCID 21942539, compound

HRID 432006Notes

Reaction equation

HRID 432006 reaction equation
C[Sn](C)C.C[Sn](C)C.[Cl:9][C:10]1[CH:11]=[CH:12][C:13](Br)=[N:14][CH:15]=1.Br[C:18]1[O:22][C:21]([C:23]2[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=2)[C:26]#[N:27])=[CH:20][CH:19]=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>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C:18]2[O:22][C:21]([C:23]3[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=3)[C:26]#[N:27])=[CH:20][CH:19]=2)=[N:14][CH:15]=1

Participants

5

Reactant 3

HCID 8170982-Bromo-5-chloropyridineHCID 6327618HexamethylditinHCID 219426553-(5-Bromofuran-2-yl)-benzonitrile

Product 1

HCID 21942539HCID 21942539, compoundYield 17.5%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst2×

Conditions

Temperature
80 °C

Procedure

Pd(PPh3)4 (5 mg, 0.004 mmol) was added to a solution of hexamethylditin (160 mg, 0.49 mmol) and 5-chloro-2-bromopyridine (76 mg, 0.395 mmol) in toulene (1 mL) under argon. The resulting solution was stirred at 80° C. for 16 h. After cooling to room temperature, a second portion of Pd(PPh3)4 (20 mg, 0.019 mmol) and 3-(5-bromofuran-2-yl)-benzonitrile (79 mg, 0.32 mmol) were added and the resulting solution was stirred at 110° C. for 14 h. After cooling to room temperature, the solvent was removed in vacuo. Chromatography (5g silica gel SPE tube, 25-50% chloroform in hexane to 2% ethyl acetate in 1:1 chloroform:hexane) followed by triturating with hexanes and purification by preparative TLC (90% dichloromethane in hexane) afforded 15.7 mg (17%) of 3-(5-(5-choro-2-pyridyl)-2-furyl)-benzonitrile (97.5% pure by GC/MS, contaminated with 2.5% dimer). 1H-NMR (CDCl3), δ (ppm): 8.55 (d, 1H), 8.03 (s, 1H), 7.94 (dd, 1H), 7.73 (s, 2H), 7.54 (m, 12), 7.16 (d, 1H), 6.88 (d, 1H).

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringthe resulting solution was stirred at 110° C. for 14 h
  3. temperatureAfter cooling to room temperature
  4. customthe solvent was removed in vacuo
  5. customby triturating with hexanes and purification by preparative TLC (90% dichloromethane in hexane)

Sources & evidence

ORD record
ord-715d4fdcfa144b15a2adb12385310f9f
Source dataset
uspto-grants-2003_12
Patent number
US06660753B2

Reaction notes

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