hexahydrate (2.26 g, 9.51 mmol) in MeOH–THF = 1 : 1 (20 mL)
under an N2 atmosphere at 0 ЊC, and the whole was refluxed
for 2 h. The solvent was evaporated off, then water (20 mL)
was added to the residue. The mixture was extracted with
CHCl3. The organic layer was dried over anhydrous sodium
sulfate and evaporated to give an oily residue. The crude
product was purified by column chromatography (CHCl3–
MeOH = 20 : 1) on silica gel to give 25 (202 mg, 62%) as a pale
yellow viscous material; νmax (CHCl3) 2918, 1601, 1457, 1241,
1099, 834 cmϪ1; δH (CDCl3) 0.25 [s, 6H, Si(CH3)2], 1.03 [s, 9H,
SiC(CH3)3], 3.33 (s, 3H, NCH3), 3.75 (s, 3H, OCH3), 3.76 (s, 3H,
OCH3), 3.81 (s, 3H, OCH3), 3.82 (s, 2H, ArCH2Im), 3.84
(s, 2H, ArCH2Im), 6.21 (d, 1H, J = 8.6 Hz, Ar–H), 6.36 (d, 1H,
J = 8.6 Hz, Ar–H), 6.77 (d, 2H, J = 8.6 Hz, Ar–H), 7.16 (d,
2H, J = 8.6 Hz, Ar–H), 7.37 (s, 1H, Im–H); δ (CDCl3) Ϫ4.1,
18.8, 23.0, 26.1, 31.4, 33.0, 55.2, 55.8, 60.3, 104.8, 113.7, 122.5,
122.7, 125.1, 129.5, 133.0, 136.6, 139.2, 146.8, 152.1, 157.7
[HRMS m/z Calc. for C27H38N2O4Si: M, 482.2601. Found: Mϩ,
482.2592].
2-Azido-5-[1-(2-hydroxy-3,4-dimethoxyphenyl)methyl]-4-
[1-(4-methoxyphenyl)methyl]-1-methyl-1H-imidazole (31)
A solution of TBAF in THF (1 M; 1.00 mL, 1.00 mmol) was
added dropwise to a solution of 30 (476 mg, 0.91 mmol) in
THF (5 mL) at room temperature. The mixture was stirred for
5 min at room temperature. Water (2 mL) was added, and the
mixture was extracted with AcOEt. The organic layer was dried
over anhydrous sodium sulfate and evaporated to give an oily
residue. The crude product was purified by column chromato-
graphy (CHCl3–MeOH = 50 : 1) on silica gel to give 31, yellow
crystals (322 mg, 87%), mp 140 ЊC dec. (recrystallized from
CHCl3–n-hexane); νmax (CHCl3) 3475, 2924, 2121, 1607, 1500,
1458, 1240, 1169, 1093 cmϪ1; δH (CDCl3) 3.13 (s, 3H, NCH3),
3.76 (s, 3H, OCH3), 3.78 (s, 2H, ArCH2Im), 3.816 (s, 3H,
OCH3), 3.823 (s, 2H, ArCH2Im), 3.89 (s, 3H, OCH3), 6.31 (d,
1H, J = 8.8 Hz, Ar–H), 6.38 (d, 1H, J = 8.6 Hz, Ar–H), 6.78 (d,
2H, J = 8.8 Hz, Ar–H), 7.16 (d, 2H, J = 8.8 Hz, Ar–H);
δ (CDCl3) 22.4, 29.3, 32.6, 55.2, 55.8, 60.9, 103.5, 113.7, 117.1,
123.3, 124.4, 129.4, 132.8, 135.2, 136.2, 138.8, 146.9, 150.9,
157.8 [HRMS m/z Calc. for C21H23N5O4: M, 409.1750. Found:
Mϩ, 409.1749].
2-Bromo-5-[1-(2-tert-butyldimethylsiloxy-3,4-dimethoxyphenyl)-
methyl]-4-[1-(4-methoxyphenyl)methyl]-1-methyl-1H-imidazole
(29)
Naamine C 2
A mixture of 31 (52 mg, 0.13 mmol) and 10% Pd/C (10 mg) in
EtOH (3 mL) was stirred for 24 h under an H2 atmosphere at
room temperature. The catalyst was removed by filtration with
CHCl3 and the filtrate was evaporated to give an oily residue.
The crude product was purified by column chromatography
(CHCl3 : MeOH = 5 : 1) on silica gel to give 2 as a yellow
powder1f,10 (47 mg, 97%); νmax (CHCl3) 3251, 3107, 2932, 1660,
1608, 1504, 1458, 1236, 1093 cmϪ1; δH (CDCl3) 3.25 (s, 3H,
NCH3), 3.736 (br s, 2H, ArCH2Im), 3.742 (s, 3H, OCH3), 3.75
(br s, 2H, ArCH2Im), 3.83 (s, 3H, OCH3), 3.89 (s, 3H, OCH3),
6.35 (d, 1H, J = 8.6 Hz, Ar–H), 6.47 (d, 1H, J = 8.6 Hz, Ar–H),
6.77 (d, 2H, J = 8.8 Hz, Ar–H), 7.10 (d, 2H, J = 8.8 Hz, Ar–H);
δ (CDCl3) 22.1, 29.7, 29.9, 55.2, 55.8, 61.0, 103.7, 114.0, 115.9,
120.9, 123.3, 124.7, 129.5, 130.1, 135.5, 146.7, 147.2, 151.3,
158.2 [HRMS m/z Calc. for C21H25N3O4: M, 383.1845. Found:
Mϩ, 383.1843].
NBS (9 mg, 0.05 mmol) was added to a solution of 25 (25 mg,
0.05 mmol) in THF (0.5 ml) under an N2 atmosphere at 0 ЊC,
and then the whole was stirred for 1 h at 0 ЊC. Then water
(0.5 ml) was added, and the mixture was extracted with AcOEt.
The organic layer was dried over anhydrous sodium sulfate and
evaporated to give an oily residue. The crude product was puri-
fied by column chromatography (AcOEt–n-hexane = 1 : 2) on
silica gel to give 29 (17 mg, 59%) as a pale yellow viscous
material; νmax (CHCl3) 2917, 1602, 1460, 1244, 1098, 834 cmϪ1
;
δH (CDCl3) 0.24 [s, 6H, Si(CH3)2], 1.02 [s, 9H, SiC(CH3)3], 3.27
(s, 3H, NCH3), 3.76 (s, 6H, 2 × OCH3), 3.810 (s, 2H, ArCH2Im),
3.813 (s, 3H, OCH3), 3.83 (s, 2H, ArCH2Im), 6.24 (d, 1H, J =
8.6 Hz, Ar–H), 6.38 (d, 1H, J = 8.6 Hz, Ar–H), 6.77 (d, 2H, J =
8.8 Hz, Ar–H), 7.15 (d, 2H, J = 8.8 Hz, Ar–H); δ (CDCl3) Ϫ4.1,
18.8, 23.9, 26.1, 32.0, 33.0, 55.2, 55.8, 60.3, 104.9, 113.7, 118.3,
121.9, 122.5, 128.3, 129.5, 132.5, 139.7, 139.8, 146.8, 152.2,
157.8 [MS m/z (% base): 562 (2), 560 (2), 507 (2), 506 (8), 505
(28), 504 (8), 503 (26), 383 (10), 381 (10), 279 (6), 209 (6), 121
(100). HRMS m/z Calc. for C27H37BrN2O4Si: M, 560.1705.
Found: Mϩ, 560.1714].
Pyronaamidine 4
A solution of 1-methylparabanic acid 32 (30 mg, 0.24 mmol)
and N,N-diisopropylethylamine (0.11 mL, 0.61 mmol) and tri-
methylsilyl chloride (0.06 mL, 0.49 mmol) in CHCl3 (0.5 mL)
was stirred for 5 min under an N2 atmosphere at 0 ЊC, and then
the stirring was continued for 2 h at room temperature. A
solution of naamine C 2 (90 mg, 0.24 mmol) in CHCl3 (0.5 mL)
was added to the mixture, the whole was refluxed for 48 h.
The solution was evaporated to give an oily residue, which was
purified by column chromatography (CHCl3–MeOH = 5 : 1)
on silica gel to afford 4, yellow crystals (32 mg, 28%), mp
182.3–184.5 ЊC (recrystallized from CHCl3–n-hexane; lit.1e,12
mp 185–187 ЊC); νmax (CHCl3) 3476, 2977, 1783, 1732, 1659,
1609, 1563, 1504, 1457, 1388, 1297, 1240, 1172, 1144, 1094,
1031 cmϪ1; δH (CD2Cl2) 3.09 (s, 3H, NCH3), 3.54 (s, 3H,
–OCH3), 3.75 (s, 3H, –OCH3), 3.80 (s, 3H, –OCH3), 3.87 (s, 3H,
–OCH3), 3.88 (s, 2H, ArCH2Im), 3.90 (s, 2H, ArCH2Im), 6.35
(d, 1H, J = 8.6 Hz, Ar–H), 6.44 (d, 1H, J = 8.6 Hz, Ar–H), 6.79
(d, 2H, J = 8.8 Hz, Ar–H), 7.10 (d, 2H, J = 8.8 Hz, Ar–H);
δ (CD2Cl2) 23.2, 24.7, 30.0, 32.2, 55.5, 56.1, 61.2, 104.0, 114.1,
116.4, 123.7, 126.9, 129.7, 131.9, 135.2, 135.8, 146.5, 146.8,
147.5, 151.6, 156.4, 158.5, 162.7 [Calc. For C25H27N5O6ؒ½H2O:
C, 59.75; H, 5.62; N, 13.94. Found: C, 59.56; H, 5.53; N,
13.81%. HRMS m/z Calc. for C25H27N5O6: M, 493.1961.
Found: Mϩ, 493.1974].
2-Azido-5-[1-(2-tert-butyldimethylsiloxy-3,4-dimethoxyphenyl)-
methyl]-4-[1-(4-methoxyphenyl)methyl]-1-methyl-1H-imidazole
(30)
A solution of tert-BuLi in n-pentane (1.56 M; 0.43 mL,
0.66 mmol) was added dropwise to a solution of 29 (124 mg,
0.22 mmol) under an N2 atmosphere at Ϫ78 ЊC. The mixture
was stirred for 15 min at Ϫ78 ЊC, then trisyl azide (205 mg,
0.66 mmol) was added, and then the whole was stirred for
1 h at Ϫ78 ЊC. Water (1 mL) was added, and the mixture
was extracted with AcOEt. The organic layer was dried over
anhydrous sodium sulfate and evaporated to give an oily resi-
due. The crude product was purified by column chromato-
graphy (AcOEt–n-hexane = 1 : 3) on silica gel to give 30 (90 mg,
78%) as a pale yellow viscous material; νmax (CHCl3) 2916, 2120,
1601, 1499, 1245, 1098, 834 cmϪ1; δH (CDCl3) 0.23 [s, 6H,
Si(CH3)2], 1.01 [s, 9H, SiC(CH3)3], 3.07 (s, 3H, NCH3), 3.746 (s,
3H, OCH3), 3.753 (s, 2H, ArCH2Im), 3.76 (s, 3H, OCH3), 3.79
(s, 2H, ArCH2Im), 3.81 (s, 3H, OCH3), 6.27 (d, 1H, J = 8.6 Hz,
Ar–H), 6.37 (d, 1H, J = 8.6 Hz, Ar–H), 6.78 (d, 2H, J = 8.8 Hz,
Ar–H), 7.16 (d, 2H, J = 8.8 Hz, Ar–H); δ (CDCl3) Ϫ4.1, 18.8,
23.3, 26.1, 29.2, 32.7, 55.2, 55.8, 60.3, 104.9, 113.7, 122.4, 122.5,
124.5, 129.4, 132.7, 136.5, 138.9, 139.7, 146.8, 152.1, 157.8
[HRMS m/z Calc. for C27H37N5O4Si: M, 523.2614. Found: Mϩ,
523.2612].
Acknowledgements
This research was financially supported, in part, by a Grant-
In-Aid for the promotion of the advancement of education and
J. Chem. Soc., Perkin Trans. 1, 2002, 1061–1066
1065