Toluene → 2-Bromo-6-(2-pyridin-3-yl-thiazol-5-yl)-pyridine

HRID 1854620Notes

Reaction equation

HRID 1854620 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.C([Sn](CCCC)(CCCC)[C:14]1[S:18][C:17]([C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)=[N:16][CH:15]=1)CCC.C(Cl)Cl.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.O>[Br:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:14]2[S:18][C:17]([C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)=[N:16][CH:15]=2)[N:3]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 6344DichloromethaneHCID 122742,6-DibromopyridineHCID 673254043-(5-Tributylstannanyl-thiazol-2-yl)-pyridine

Product 1

HCID 533113132-Bromo-6-(2-pyridin-3-yl-thiazol-5-yl)-pyridineYield 35%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A sealed tube was charged with 2,6-dibromopyridine (269 mg, 1.13 mmol), 3-(5-tributylstannanyl-thiazol-2-yl)-pyridine (511 mg, 1.13 mmol), Pd(PPh3)4 (131 mg, 0.11 mmol), [1,1-Bis(diphenylphosphino)ferrocene]palladium(II) chloride. CH2Cl2 (20 mg, 0.024 mmol) and anhydrous and degassed toluene (5 ml) and heated to 110° C. with stirring for 36 h. The cooled reaction mixture was treated with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered and evaporated under reduced pressure before purification by column chromatography on SiO2 using combiflash Companion®, eluting with cyclohexane/ethyl acetate to afford the title compound as a white solid (125 mg, 35%). 1H NMR (DMSO-d6, 300 MHz): δ=9.21 (d, J=1.7 Hz, 1H), 8.72 (s, 1H), 8.70 (m, 1H), 8.39 (m, 1H), 8.14 (d, J=7.8 Hz, 1H), 7.88 (dd, J=8.0; 7.8 Hz, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.57 (m, 1H).

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure before purification by column chromatography on SiO2 using combiflash Companion®
  7. washeluting with cyclohexane/ethyl acetate

Sources & evidence

ORD record
ord-e66f448996fb4263bc92e301dadb0978
Source dataset
uspto-grants-2015_02
Patent number
US08962665B2

Reaction notes

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