Acetic Acid → 1,4-Dibutyl-3-{6-[2-(1H-tetrazol-5-yl)-phenyl]-pyridin-3-ylmethyl}-1,3-dihydro-imidazol-2-one

HRID 1756722Notes

Reaction equation

HRID 1756722 reaction equation
C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3B(O)O)=[N:11][N:10]=[N:9]2)C=CC=CC=1.[CH2:34]([N:38]1[CH:42]=[C:41]([CH2:43][CH2:44][CH2:45][CH3:46])[N:40]([CH2:47][C:48]2[CH:49]=[N:50][C:51](Br)=[CH:52][CH:53]=2)[C:39]1=[O:55])[CH2:35][CH2:36][CH3:37].C(=O)([O-])[O-].[Na+].[Na+].C(O)(=O)C>C(O)C.C1(C)C=CC=CC=1.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>[CH2:34]([N:38]1[CH:42]=[C:41]([CH2:43][CH2:44][CH2:45][CH3:46])[N:40]([CH2:47][C:48]2[CH:49]=[N:50][C:51]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]3[NH:8][N:9]=[N:10][N:11]=3)=[CH:52][CH:53]=2)[C:39]1=[O:55])[CH2:35][CH2:36][CH3:37]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 103427452-(1-Trityl-1H-tetrazol-5-YL)phenylboronic acidHCID 154057291,4-dibutyl-1,3-dihydro-3-[(6-bromo-3-pyridinyl)methyl]-2H-imidazol-2-one

Product 1

HCID 1784412521,4-Dibutyl-3-{6-[2-(1H-tetrazol-5-yl)-phenyl]-pyridin-3-ylmethyl}-1,3-dihydro-imidazol-2-oneYield 43%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent2×HCID 1140TolueneSolvent2×

Procedure

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 2 M 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. Recrystatlization 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) δ0.88 (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 (tel intensity) 432 (100), 404 (18), (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.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. concentrationthe reaction concentrated in vacuo
  4. customThe product was purified by silica gel chromatography (Waters Prep-500A)
  5. customthe acetonitrile removed in vacuo
  6. extractionthe water extracted 4 times with chloroform
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d0401db230474d06b95e4a818816e91c
Source dataset
uspto-grants-1995_08
Patent number
US05441970

Reaction notes

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