pressure. The resulting residue was purified by column chromatography to give 390 mg
1
compound 13 as a yellow solid. Yield: 72.3%. H NMR (400MHz, CDCl , ppm) ꢀ: 7.65-7.33
3
(
m, 6H), 7.13 (d, 2H), 5.92 (s, 1H), 5.22 (s, 2H), 4.41 (s, 2H), 3.98-3.92 (m, 4H), 2.47 (t, 2H),
+
.57 (m, 2H), 1.26 (m, 2H), 0.87 (t, 3H). MS (ESI): [M + H] calcd 455.2; found 455.3.
1
4
'-((2-butyl-4-chloro-5-(1,3-dioxolan-2-yl)-1H-imidazol-1-yl)methyl)-N'-((isobutoxycarbo
nyl)oxy)-[1,1'-biphenyl]-2-carboximidamide(14)
A solution of compound 13 (500 mg, 1.10 mmol) in DMF (50 mL) was treated with isobutyl
o
chloroformate (180 mg, 1.32 mmol) and pyridine (174 mg, 2.20 mol) at 0 C and stirred for 6
h under nitrogen. After the reaction was completed, the resulting mixture was diluted with
water and extracted with ethyl acetate (30 mL × 4). The organic layer was washed with
saturated salt water (40 mL × 4) and dried over MgSO
4
. After filtration, the solvent was
removed under reduced pressure. The residue was purified by column chromatography to give
1
2
7
2
3
52 mg compound 14 as a yellow solid. Yield: 41.3%. H NMR (400MHz, CDCl , ppm) ꢀ:
.67-7.34 (m, 6H), 7.14 (d, 2H), 5.92 (s, 1H), 5.24 (s, 2H), 4.03 (d, 2H), 4.04-3.95 (m, 4H),
.54 (t, 2H), 2.04-2.00 (m, 1H), 1.59 (m, 2H), 1.28 (m, 2H), 0.97 (d, 6H), 0.83 (t, 3H). MS
+
ESI): [M + H] calcd 455.2; found 555.3.
(
3
-(4'-((2-butyl-4-chloro-5-(1,3-dioxolan-2-yl)-1H-imidazol-1-yl)methyl)-[1,1'-biphenyl]-2
-
yl)-1,2,4-oxadiazol-5(4H)-one(15)
A solution of compound 14 (500 mg, 0.90 mmol) in xylene (50 mL) was refluxed for 6 h
under nitrogen. After the reaction was completed, the solvent was removed under reduced
pressure. The residue was purified by column chromatography to give 400 mg compound 15
1
as a yellow solid. Yield: 92.8%. H NMR (400 MHz, CDCl
3
,) ꢀ: 7.82-7.00 (m, 8H), 5.79 (s,
H), 5.22 (s, 2H), 3.89 (s, 4H), 2.38 (t, 2H), 1.52 (m, 2H), 1.25 (m, 2H), 0.82 (t, 3H). MS
1
+
(
ESI): [M + H] calcd 481.2; found 481.3.
-butyl-4-chloro-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)met
2
hyl)-1H-imidazole-5-carbaldehyde(2)
A solution of compound 15 (500 mg, 1.04 mmol) in DCM (50 mL) was treated with PPTS
(
261 mg, 1.04 mmol) and stirred at r.t. for 3 h. After the reaction was completed, the resulting
mixture was diluted with water and extracted with ethyl acetate (30 mL × 4). The organic
layer was washed with saturated salt water (40 mL × 4) and dried over MgSO . After filtration,
4
the solvent was removed under reduced pressure. The residue was purified by column
1
chromatography to give 303 mg 2 as a yellow solid. Yield: 66.8%. H NMR (400 MHz,
DMSO, ppm) ꢀ: 9.65 (s, 1H), 8.95 (s, H), 7.78-7.08 (m, 8H), 5.54 (s, 2H), 2.66 (t, 2H), 1.69
+
m, 2H), 1.36 (m, 2H), 0.90 (t, 3H). MS(ESI): [M + H] calcd 437.2; found 437.3. IR (KBr,
(
-1
cm ): 3431.17, 2959.71, 2860.32, 2745.12, 2667.68, 1773.81, 1670.76, 1598.95, 1522.89,
1492.38, 1462.05, 1378.28, 1278.41, 1221.56, 941.26, 868.10, 763.50, 723.22.
2
-butyl-4-chloro-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)met
hyl)-1H-imidazole-5-carboxylic acid(3)
A solution of compound 2 (500 mg, 1.14 mmol) in butanol (50 mL) was treated with NaClO
2
(
2 4
1.03 g, 11.4 mmol) and NaH PO (1.37 g, 11.4 mmol) in 20 mL water, and the solution was
stirred at r.t. for 5 h. After the reaction was completed, the resulting mixture was diluted with
water and extracted with ethyl acetate (30 mL × 4). The organic layer was washed with
saturated salt water (40 mL × 4) and dried over MgSO
4
. After filtration, the solvent was
removed under reduced pressure. The residue was purified by column chromatography to give