Tributyltin Chloride → 7-(1-Methyl-1-triethylsilanyloxyethyl)-3-(2-trifluoromethylpyrimidin-4-yl)imidazo[1,2-alpha]pyrimidine

HRID 1796056Notes

Reaction equation

HRID 1796056 reaction equation
C([Mg]Cl)(C)C.Br[C:7]1[N:11]2[CH:12]=[CH:13][C:14]([C:16]([CH3:26])([O:18][Si:19]([CH2:24][CH3:25])([CH2:22][CH3:23])[CH2:20][CH3:21])[CH3:17])=[N:15][C:10]2=[N:9][CH:8]=1.C([Sn](Cl)(CCCC)CCCC)CCC.Cl[C:42]1[CH:47]=[CH:46][N:45]=[C:44]([C:48]([F:51])([F:50])[F:49])[N:43]=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>[CH3:17][C:16]([C:14]1[CH:13]=[CH:12][N:11]2[C:7]([C:42]3[CH:47]=[CH:46][N:45]=[C:44]([C:48]([F:51])([F:50])[F:49])[N:43]=3)=[CH:8][N:9]=[C:10]2[N:15]=1)([O:18][Si:19]([CH2:24][CH3:25])([CH2:22][CH3:23])[CH2:20][CH3:21])[CH3:26]

Participants

7

Reactant 4

HCID 15096Tributyltin ChlorideHCID 152943694-Chloro-2-(trifluoromethyl)pyrimidineHCID 695598483-Bromo-7-(1-methyl-1-triethylsilanyloxyethyl)imidazo[1,2-alpha]pyrimidineHCID 178418918HCID 178418918, compound

Product 1

HCID 695604937-(1-Methyl-1-triethylsilanyloxyethyl)-3-(2-trifluoromethylpyrimidin-4-yl)imidazo[1,2-alpha]pyrimidineYield 31.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of isopropylmagnesium chloride (2.0M in THF, 525 μl, 1.05 mmol) was added dropwise to a stirred suspension of 3-bromo-7-(1-methyl-1-triethylsilanyloxyethyl)imidazo[1,2-α]pyrimidine (370 mg, 1.0 mmol) in THF (5 ml) at −78° C. under N2. The resulting solution was stirred at −78° C. for 15 min and then tributyltin chloride (298 μl, 1.1 mmol) was added. The reaction was warmed to 0° C. and stirred for 1 h. 4-Chloro-2-trifluoromethylpyrimidine (200 mg, 1.1 mmol) and tetrakis(triphenylphosphine)palladium(0) (110 mg, 10 mol %) were added and the reaction heated at reflux for 18 h. The mixture was concentrated under reduced pressure while dry loading onto silica and then purified by column chromatography on silica using 50-80% EtOAc/isohexanes as the eluent to afford 7-(1-methyl-1-triethylsilanyloxyethyl)-3-(2-trifluoromethylpyrimidin-4-yl)imidazo[1,2-α]pyrimidine (136 mg): 1H NMR (400 MHz, CDCl3) δ 10.10 (1H, d, J 7.4), 8.82 (1H, d, J 5.5), 8.57 (1H, s), 7.78 (1H, d, J 5.5), 7.67 (1H, d, J 7.4), 1.70 (6H, s), 1.00 (9H, t, J 8.0), 0.68 (6H, q, J 8.0); m/z (ES+) 438 (M+H+).

Workup

  1. temperatureThe reaction was warmed to 0° C.
  2. stirringstirred for 1 h
  3. temperaturethe reaction heated
  4. temperatureat reflux for 18 h
  5. concentrationThe mixture was concentrated under reduced pressure
  6. customwhile dry loading onto silica
  7. custompurified by column chromatography on silica using 50-80% EtOAc/isohexanes as the eluent

Sources & evidence

ORD record
ord-f4f168a489174c818b293a48f2cd33fb
Source dataset
uspto-grants-2006_04
Patent number
US07030128B2

Reaction notes

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