Imidazole → 3-[2-(Imidazol-1-yl)pyrimidin-4-yl]-7-(1-methyl-1-triethylsilanyloxyethyl)imidazo[1,2-alpha]pyrimidine

HRID 1796059Notes

Reaction equation

HRID 1796059 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH:11]1[CH:15]=[CH:14][N:13]=[CH:12]1.Cl[C:17]1[N:22]=[C:21]([C:23]2[N:27]3[CH:28]=[CH:29][C:30]([C:32]([CH3:42])([O:34][Si:35]([CH2:40][CH3:41])([CH2:38][CH3:39])[CH2:36][CH3:37])[CH3:33])=[N:31][C:26]3=[N:25][CH:24]=2)[CH:20]=[CH:19][N:18]=1>C1COCC1>[N:11]1([C:17]2[N:22]=[C:21]([C:23]3[N:27]4[CH:28]=[CH:29][C:30]([C:32]([CH3:33])([O:34][Si:35]([CH2:36][CH3:37])([CH2:40][CH3:41])[CH2:38][CH3:39])[CH3:42])=[N:31][C:26]4=[N:25][CH:24]=3)[CH:20]=[CH:19][N:18]=2)[CH:15]=[CH:14][N:13]=[CH:12]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 2733832Lithium HexamethyldisilazideHCID 878895493-(2-Chloropyrimidin-4-yl)-7-(1-methyl-1-triethylsilanyloxyethyl)-imidazo[1,2-alpha]pyrimidine

Product 1

HCID 695607033-[2-(Imidazol-1-yl)pyrimidin-4-yl]-7-(1-methyl-1-triethylsilanyloxyethyl)imidazo[1,2-alpha]pyrimidineYield 45.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of LiHMDS (370 μl) in hexanes (1.0M, 370 μmol) was added to a stirred solution of imidazole (25 mg, 0.37 mmol) and 3-(2-chloropyrimidin-4-yl)-7-(1-methyl-1-triethylsilanyloxyethyl)imidazo[1,2-α]pyrimidine (from Example 34) (150 mg, 0.37 mmol) in THF (5 ml) at −78° C. under N2. The reaction was allowed to warm slowly to room temperature overnight and was then quenched with NH4Cl solution (10 ml). The organics were extracted with EtOAc (2×25 ml), washed with brine (10 ml) and concentrated under reduced pressure while dry loading onto silica. The residue was purified by column chromatography on silica using 100% EtOAc as the eluent to afford 3-[2-(imidazol-1-yl)pyrimidin-4-yl]-7-(1-methyl-1-triethylsilanyloxyethyl)imidazo[1,2-α]pyrimidine (73 mg, 45%): 1H NMR (400 MHz, d6-DMSO) δ 10.08 (1H, d, J 7.2), 8.93 (1H, s), 8.85-8.78 (2H, m), 8.13 (1H, d, J 1.1), 8.03 (1H, d, J 5.5), 7.72 (1H, d, J 7.2), 7.21 (1H, s), 1.64 (6H, s), 0.96 (9H, t, J 8.0), 0.65 (6H, q, J 8.0); m/z (ES+) 453 (M+H+).

Workup

  1. customwas then quenched with NH4Cl solution (10 ml)
  2. extractionThe organics were extracted with EtOAc (2×25 ml)
  3. washwashed with brine (10 ml)
  4. concentrationconcentrated under reduced pressure
  5. customwhile dry loading onto silica
  6. customThe residue was purified by column chromatography on silica using 100% EtOAc as the eluent

Sources & evidence

ORD record
ord-66a5b6fe6cb0473e81cd21c9bd7d6929
Source dataset
uspto-grants-2006_04
Patent number
US07030128B2

Reaction notes

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