Reaktion #460802

Reaktionsgleichung

acetic acid

2-(N-triphenylmethyltetrazol-5-yl)phenylboronic acid

1,4-dibutyl-1,3-dihydro-3-[(6-bromo-3-pyridinyl)methyl]-2H-imidazol-2-one

sodium carbonate

→

1,4-dibutyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one

Ausbeute 43.0%

Lösungsmittel

ethanol

toluene

ethanol

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was heated
2. 2
   Temperaturto reflux
3. 3
   Einengenthe reaction concentrated in vacuo
4. 4
   SonstigeThe product was purified by silica gel chromatography (Waters Prep-500A)
5. 5
   Sonstigethe acetonitrile removed in vacuo
6. 6
   Extraktionthe water extracted 4 times with chloroform
7. 7
   Trocknendried (MgSO4)
8. 8
   Einengenconcentrated in vacuo
9. 9
   SonstigeRecrystallization from ethyl acetate

Vorschrift

A solution of 21.7 g (50.2 mmol) of 2-(N-triphenylmethyltetrazol-5-yl)phenylboronic acid from step 6 in 80 mL of ethanol and 130 mL of toluene was added to a mixture of 5 g (4 mmol) of tetrakis(triphenylphosphine) Pd(0), 16.75 g (45.8 mmol) of 1,4-dibutyl-1,3-dihydro-3-[(6-bromo-3-pyridinyl)methyl]-2H-imidazol-2-one from step 5, 225 mL of toluene, 100 mL of 2M sodium carbonate, and 150 mL of ethanol. The reaction mixture was heated to reflux and vigorously stirred under nitrogen for 14 h. The pH was adjusted to 6 with acetic acid and the reaction concentrated in vacuo. The product was purified by silica gel chromatography (Waters Prep-500A) using 2-propanol/methylene chloride (0-50%) followed by reverse phase chromatography (Waters Deltaprep-3000) using acetonitrile/water (30-35:70-65) (0.05% TFA). The pure fractions (by analytical HPLC) were combined, the acetonitrile removed in vacuo, and the water extracted 4 times with chloroform. The extracts were combined, dried (MgSO4), and concentrated in vacuo. Recrystallization from ethyl acetate gave 8.5 g (43%) of colorless 1,4-dibutyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one as a colorless solid: mp 170-171° C.; NMR (CDCl3) δ 0.88 (t, J=7 Hz, 3H), 0.96 (t, J=7 Hz, 3H), 1.28-1.54 (m, 6H), 1.61-1.72 (m, 2H), 2.28 (t, J=8 Hz, 2H), 3.63 (t, J=7 Hz, 2H), 4.96 (s, 2H), 5.96 (s, 1H), 7.36 (d, J=9 Hz, 1H), 7.47-7.58 (m, 3H), 7.67 (dd, J=9 and 2 Hz, 1H), 8.06-8.13 (m, 1H), 8.52 (d, J,=2 Hz, 1H); MS (FAB) m/e (rel intensity) 432 (100), 404 (18), 237 (14), 209 (92), 180 (82); HRMS. Calc'd for M+H: 432.2512 Found: 432.2554. Anal. Calc'd for C24H29N7O: C, 66.80; H, 6.77; N, 22.72. Found: C, 66.59; H, 6.85; N, 22.57.

Quelle