4-Iodo-1-tritylimidazole → 2-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine

HRID 42298

Reaction equation

HRID 42298 reaction equation
I[C:2]1[N:3]=[CH:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.C([Mg]Br)C.Br[C:31]1[CH:32]=[N:33][C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[N:35][CH:36]=1>C1COCC1.ClCCl.[Cl-].[Zn+2].[Cl-].[Pd]>[C:37]1([C:34]2[N:33]=[CH:32][C:31]([C:2]3[N:3]=[CH:4][N:5]([C:7]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:6]=3)=[CH:36][N:35]=2)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

8

Reactant 3

HCID 6182524-Iodo-1-tritylimidazoleHCID 143877455-Bromo-2-phenylpyrimidineHCID 178418443HCID 178418443, compound

Product 1

HCID 592524592-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 3007855ZincchlorideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 4-Iodo-1-trityl-1H-imidazole (Synthonix, 2.0 g, 4.58 mmol) in THF (50 mL) at room temperature was added ethylmagnesium bromide (Aldrich, 1.0 M solution in THF, 5.5 mL, 5.50 mmol) under dry conditions. After stirring for 90 minutes, zinc chloride (Aldrich, 0.749. g, 5.50 mmol) was added to the reaction mixture. After stirring for an additional 90 minutes, tetrakis(triphenyl)phosphine)palladium (Strem, 0.529 g, 0.46 mmol) and 5-bromo-2-phenylpyrimidine (as prepared in Example 1, step A, 1.29 g, 5.50 mmol) were added to the reaction mixture. The reaction mixture was heated in a 70° C. oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with 0.5 M EDTA buffer (at pH ˜9) (2×250 mL) followed by brine (150 mL). The organics were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash silica column chromatography using an 80 g Silicycle® column (elution with 10-30% ethyl acetate in hexane) which afforded the desired intermediate, 2-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine, as a white solid (1.38 g, 65%). Rf 0.87 with 95:5 v/v dichloromethane-methanol; 1H-NMR (400 MHz; DMSO-d6) δ 9.29 (s, 2H), 8.42 (m, 2H), 7.92 (d, 1H), 7.62 (d, 1H), 7.56-7.43 (m, 13H), 7.24-7.22 (m, 6H); MS (ESI−) m/z 463.0 (M−1); H-PGDS FPBA IC50: >20 μM.

Workup

  1. stirringAfter stirring for an additional 90 minutes
  2. temperatureUpon cooling
  3. washwashed with 0.5 M EDTA buffer (at pH ˜9) (2×250 mL)
  4. dry with materialThe organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash silica column chromatography
  8. washan 80 g Silicycle® column (elution with 10-30% ethyl acetate in hexane) which

Sources & evidence

ORD record
ord-4efe0042766d459ab4f9c536c728c18f
Source dataset
uspto-grants-2013_09
Patent number
US08536185B2

Linked notes

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