Toluene → HCID 53311314, compound

HRID 1854622Notes

Reaction equation

HRID 1854622 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.[O:9]1[CH2:13][CH2:12][O:11][CH:10]1[C:14]1[S:15][C:16]([Sn](CCCC)(CCCC)CCCC)=[CH:17][N:18]=1.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:16]2[S:15][C:14]([CH:10]3[O:11][CH2:12][CH2:13][O:9]3)=[N:18][CH:17]=2)[N:3]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 6344DichloromethaneHCID 122742,6-DibromopyridineHCID 59023582HCID 59023582, compound

Product 1

HCID 53311314HCID 53311314, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A sealed tube was charged with 2,6-dibromopyridine (525 mg, 2.21 mmol), 2-[1,3]dioxolan-2-yl-5-tributylstannanyl-thiazole (J. Med. Chem. 2007, 50, 6303) (990 mg, 2.21 mmol), Pd(PPh3)4 (256 mg, 0.22 mmol), [1,1-Bis(diphenylphosphino)ferrocene]palladium(II) chloride. CH2Cl2 (30 mg, 0.036 mmol) and anhydrous and degassed toluene (8 ml) and heated to 110° C. with stirring for 48 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 100/0 to 44/56 to afford the title compound as a white solid (370 mg, 54%). 1H NMR (DMSO-d6, 300 MHz): δ=8.55 (s, 1H), 8.06 (dd, J=7.7-0.7 Hz, 1H), 7.85 (dd, J=7.9-7.7 Hz, 1H), 7.61 (dd, J=7.9-0.7 Hz, 1H), 6.08 (s, 1H), 4.15-4.00 (m, 4H).

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 100/0 to 44/56

Sources & evidence

ORD record
ord-e87b38a661af4c9eb4369e599d2a6c0a
Source dataset
uspto-grants-2015_02
Patent number
US08962665B2

Reaction notes

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