4-(4-Bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloro-4,5-dihydropyrimidine → 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-5-yl)-2-chloropyrimidine

HRID 535741Notes

Reaction equation

HRID 535741 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH:22]2[CH2:24][CH2:23]2)[N:5]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:6]=1[CH:7]1[CH2:12][CH:11]=[N:10][C:9]([Cl:13])=[N:8]1>CCOC(C)=O.[O-2].[O-2].[Mn+4]>[Br:1][C:2]1[N:3]=[C:4]([CH:22]2[CH2:24][CH2:23]2)[N:5]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:19])([CH3:20])[CH3:21])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([Cl:13])[N:8]=1

Participants

4

Reactant 1

HCID 670534874-(4-Bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloro-4,5-dihydropyrimidine

Product 1

HCID 866514084-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-5-yl)-2-chloropyrimidineYield 83%

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

4-(4-Bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloro-4,5-dihydropyrimidine (21.65 g, 50.1 mmol) and manganese dioxide (43.6 g, 501 mmol) in EtOAc (240 mL) was heated at reflux for 2.5 hours. The reaction mixture was cooled to room temperature and filtered through Celite. The filtrates were concentrated and the residue purified by flash column chromatography (10-40% EtOAc in heptane) to afford 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine as a yellow oil (17.8 g, 41.4 mmol, 83%). LCMS (m/z) 429.0 (MH+), tR=1.24 minutes; 1H NMR (400 MHz, CDCl3) δ −0.06 (s, 9H), 0.82-0.90 (m, 2H), 1.04-1.11 (m, 2H), 1.14-1.20 (m, 2H), 2.06 (m, 1H), 3.55-3.62 (m, 2H), 5.92 (s, 2H), 7.92 (d, J=5.5 Hz, 1H), 8.62 (d, J=5.5 Hz, 1H).

Workup

  1. temperatureat reflux for 2.5 hours
  2. filtrationfiltered through Celite
  3. concentrationThe filtrates were concentrated
  4. customthe residue purified by flash column chromatography (10-40% EtOAc in heptane)

Sources & evidence

ORD record
ord-bfad1d5de57a4615b689a3d0d59c1096
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

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