Tributyltin Chloride → 3-[3-(Thien-2-yl)-[1,2,4]thiadiazol-5-yl]-7-trifluoromethylimidazo[1,2-alpha]pyrimidine

HRID 1796025Notes

Reaction equation

HRID 1796025 reaction equation
C([Mg]Cl)(C)C.Br[C:7]1[N:11]2[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[N:15][C:10]2=[N:9][CH:8]=1.C([Sn](Cl)(CCCC)CCCC)CCC.Cl[C:35]1[S:39][N:38]=[C:37]([C:40]2[S:41][CH:42]=[CH:43][CH:44]=2)[N:36]=1>C1COCC1.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.[Cu]I>[S:41]1[CH:42]=[CH:43][CH:44]=[C:40]1[C:37]1[N:36]=[C:35]([C:7]2[N:11]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[N:15][C:10]3=[N:9][CH:8]=2)[S:39][N:38]=1

Participants

8

Reactant 4

HCID 15096Tributyltin ChlorideHCID 27358235-Chloro-3-(2-thienyl)-1,2,4-thiadiazoleHCID 113914623-Bromo-7-(trifluoromethyl)imidazo[1,2-a]pyrimidineHCID 178418918HCID 178418918, compound

Product 1

HCID 99031813-[3-(Thien-2-yl)-[1,2,4]thiadiazol-5-yl]-7-trifluoromethylimidazo[1,2-alpha]pyrimidineYield 26%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of iPrMgCl (2.0M in THF, 1.13 ml, 2.26 mmol) was added dropwise to a stirred suspension of 3-bromo-7-trifluoromethylimidazo[1,2-α]pyrimidine (547 mg, 2.06 mmol) in THF (20 ml) at −78° C. under N2. The resulting solution was stirred at −78° C. for 15 min and then tributyltin chloride (670 μl, 2.47 mmol) was added. The reaction was warmed to 0° C. and stirred for 1 h. 5-Chloro-3-(thien-2-yl)-[1,2,4]thiadiazole (500 mg, 2.47 mmol) and tetrakis(triphenylphosphine)palladium(0) (237 mg, 0.21 mmol) were added and the reaction heated at reflux for 1 h. Copper(I) iodide (50 mg, 0.26 mmol) was added and heating continued for a further 1.5 h. The mixture was concentrated under reduced pressure while dry loading onto silica. The resulting crude residue was purified by column chromatography on silica, using 50% EtOAc in hexane as the eluent, and subsequent recystallisation from dichloromethane/isohexanes gave 3-[3-(thien-2-yl)-[1,2,4]thiadiazol-5-yl]-7-trifluoromethylimidazo[1,2-α]pyrimidine (188 mg, 26%): δH (400 MHz, d6-DMSO) 7.30 (1H, t, J 3.7), 7.83-7.90 (2H, m), 8.11 (1H, dd, J 3.7 and 1.1), 9.14 (1H, s), 10.20 (1H, d, J 7.1); m/z (ES+) 353 (M+).

Workup

  1. temperatureThe reaction was warmed to 0° C.
  2. stirringstirred for 1 h
  3. temperaturethe reaction heated
  4. temperatureat reflux for 1 h
  5. temperatureheating
  6. waitcontinued for a further 1.5 h
  7. concentrationThe mixture was concentrated under reduced pressure
  8. customwhile dry loading onto silica
  9. customThe resulting crude residue was purified by column chromatography on silica

Sources & evidence

ORD record
ord-6668624172404d348cf871dc63e57aaa
Source dataset
uspto-grants-2006_04
Patent number
US07030128B2

Reaction notes

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