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N. Matsunaga et al. / Bioorg. Med. Chem. 12 (2004) 4313–4336
organic layers were concentrated and the residue was
purified by column chromatography on silica gel using
CHCl3–MeOH ¼ 5:1 as an eluent to give 26 (153 mg,
71%) as colourless crystals. Mp 162.5–163.5 ꢁC
(THF–hexane). IR (KBr): 3106, 2998, 1611, 1264, 1198,
AcOEt. The organic layers were combined, dried over
MgSO4 and concentrated and the residue was purified
by column chromatography on silica gel using AcOEt–
hexane ¼ 3:1 to 1:1 as an eluent to give 27i (1.04 g, 88%)
as colourless crystals. Mp 120–121 ꢁC (AcOEt). IR
(KBr): 3167, 1742, 1609, 1485, 1447, 1265, 1165, 1132,
1161, 1032, 847 cmꢀ1 1H NMR (CDCl3+CD3OD) d:
.
1
1.94 (1H, s), 3.92 (3H, s), 5.94 (1H, s), 6.69 (1H, s),
7.11–7.17 (2H, m), 7.48 (1H, dd, J ¼ 8:5, 1.7 Hz), 7.56
(1H, d, J ¼ 1:0 Hz), 7.70 (1H, s), 7.75 (1H, d,
J ¼ 1:8 Hz), 7.84 (1H, s). Anal. Calcd for C15H14N2O2:
C, 70.85; H, 5.55; N, 11.02. Found: C, 70.77; H, 5.49; N,
10.76.
1030, 889, 849, 756, 700 cmꢀ1. H NMR (DMSO-d6) d:
3.85 (3H, s), 6.49 (1H, s), 6.83 (1H, d, J ¼ 1:4 Hz), 7.11–
7.15 (7H, m), 7.25 (1H, d, J ¼ 1:4 Hz), 7.37–7.43 (13H,
m), 7.67–7.74 (3H, m), 8.44–8.47 (2H, m). Anal. Calcd
for C40H32N2O2Æ0.4H2O: C, 82.85; H, 5.70; N, 4.83.
Found: C, 82.82; H, 5.74; N, 4.67.
6.38. Introduction of alkyl or aryl group into 22. 1-(6-
Methoxy-2-naphthyl)-1-(1-trityl-1H-imidazol-4-yl)etha-
nol (27a)
6.41. (6-Methoxy-2-naphthyl)-3-pyridyl-(1-trityl-1H-imid-
azol-4-yl)methanol (27j)
Prepared from 22 and 3-bromopyridine by a similar
procedure to that described for the synthesis of 27i in
83% yield. Colourless crystals. Mp 170 ꢁC decomp
(AcOEt–hexane). IR (KBr): 3216, 1609, 1485, 1443,
To a solution of 22 (2.50 g, 5.1 mmol) in THF (20 mL)
was added methylmagnesium bromide (3.0 M solution
in Et2O, 3.4 mL, 10.1 mmol) dropwise with ice-cooling.
The mixture was stirred for 20 min, diluted with satu-
rated NH4Cl and extracted with several portions of
AcOEt. The organic layers were combined, dried over
MgSO4 and concentrated to give 27a (2.51 g, 97%) as
colourless crystals. Mp 169–170 ꢁC (AcOEt–hexane). IR
(KBr): 3150, 1605, 1493, 1445, 1264, 1177, 1165, 909,
1385, 1269, 1171, 1067, 1028, 878, 849, 748, 702 cmꢀ1
.
1H NMR (CDCl3) d: 3.90 (3H, s), 6.40 (1H, d,
J ¼ 1:4 Hz), 7.09–7.23 (9H, m), 7.27–7.41 (10H, m), 7.50
(1H, d, J ¼ 1:6 Hz), 7.57–7.65 (3H, m), 7.70–7.76 (1H,
m), 8.47 (1H, dd, J ¼ 4:8, 1.6 Hz), 8.54 (1H, d,
J ¼ 2:2 Hz). Anal. Calcd for C39H31N3O2Æ0.3H2O: C,
80.89; H, 5.50; N, 7.26. Found: C, 80.82; H, 5.50; N,
7.04.
1
747, 733, 702 cmꢀ1. H NMR (CDCl3) d: 1.85 (3H, s),
3.62 (1H, br s), 3.90 (3H, s), 6.77 (1H, d, J ¼ 1:4 Hz),
7.09 (1H, s), 7.13–7.21 (7H, m), 7.30–7.36 (9H, m), 7.41
(1H, d, J ¼ 1:4 Hz), 7.45 (1H, dd, J ¼ 8:7, 1.8 Hz), 7.62–
7.69 (2H, m), 7.80 (1H, d, J ¼ 1:6 Hz). Anal. Calcd for
C35H30N2O2: C, 82.33; H, 5.92; N, 5.49. Found: C,
82.18; H, 5.89; N, 5.39.
6.42. (6-Methoxy-2-naphthyl)-4-pyridyl-(1-trityl-1H-imid-
azol-4-yl)methanol (27k)
Prepared from 22 and 4-bromopyridine by a similar
procedure to that described for the synthesis of 27i in
75% yield. Colourless crystals. IR (KBr): 1605, 1483,
1447, 1265, 1223, 1169, 1130, 1063, 1036, 762, 748,
6.39. 1-(6-Methoxy-2-naphthyl)-2-methyl-1-(1-trityl-1H-
imidazol-4-yl)propan-1-ol (27d)
1
702 cmꢀ1. H NMR (DMSO-d6) d: 3.85 (3H, s), 6.49
Prepared from 22 and isopropylmagnesium bromide
(2.0 M solution in THF) by a similar procedure to that
described for the synthesis of 27a in 56% yield. Mp
186–187 ꢁC (ether). IR (KBr): 1605, 1483, 1445, 1264,
(1H, s), 6.83 (1H, d, J ¼ 1:4 Hz), 7.11–7.15 (7H, m), 7.25
(1H, d, J ¼ 1:4 Hz), 7.37–7.43 (13H, m), 7.67–7.74 (3H,
m), 8.44–8.47 (2H, m). Anal. Calcd for C39H31N3O2: C,
81.65; H, 5.45; N, 7.32. Found: C, 81.55; H, 5.35; N,
7.28.
1
1223, 1167, 909, 747, 733, 702 cmꢀ1. H NMR (CDCl3)
d: 0.74 (3H, d, J ¼ 6:8 Hz), 0.94 (3H, d, J ¼ 6:6 Hz),
1.90 (1H, br s), 2.46–2.59 (1H, m), 3.91 (3H, s), 6.80
(1H, d, J ¼ 1:4 Hz), 7.09–7.17 (8H, m), 7.29–7.37 (10H,
m), 7.53 (1H, dd, J ¼ 8:7, 1.7 Hz), 7.62–7.71 (2H, m),
7.93 (1H, d, J ¼ 1:2 Hz). Anal. Calcd for C37H34N2O2:
C, 82.50; H, 6.36; N, 5.20. Found: C, 82.29; H, 6.34; N,
5.22.
6.43. Deprotection of the trityl group
Compounds 28a,i,j,k and 29 were prepared from
27a,i,j,k and 22, respectively, by the procedure described
for the synthesis of 26.
6.40. (6-Methoxy-2-naphthyl)(phenyl)(1-trityl-1H-imid-
azol-4-yl)methanol (27i)
6.44. 1-(1H-Imidazol-4-yl)-1-(6-methoxy-2-naphthyl)-
ethanol (28a)
To a solution of bromobenzene (0.85 mL, 8.1 mmol) in
Et2O (20 mL) was added n-BuLi (1.6 M solution in
hexane, 5.1 mL, 8.1 mmol) dropwise at )78 ꢁC. The
stirring was continued for 20 min and a solution of 22
(1.0 g, 2.0 mmol) in THF (10 mL) was added dropwise.
The mixture was stirred at )78 ꢁC for 30 min, quenched
with water and extracted with several portions of
Yield 74%. Colourless crystals. Mp 159–160 ꢁC
(THF–hexane). IR (KBr): 3200, 1609, 1485, 1453,
1264, 1173, 1115, 1034, 905, 893, 847, 802 cmꢀ1 1H
.
NMR (CDCl3+CD3OD) d: 1.94 (3H, s), 3.92
(3H, s), 6.88 (1H, s), 7.11–7.16 (2H, m), 7.46 (1H, dd,
J ¼ 8:5, 1.9 Hz), 7.53 (1H, d, J ¼ 1:0 Hz), 7.67 (1H,
d, J ¼ 3:4 Hz), 7.72 (1H, d, J ¼ 5:2 Hz), 7.82 (1H,