N. Ando, S. Terashima / Tetrahedron 66 (2010) 6224e6237
6231
monohydrochloride (22.9 g, 240 mmol) as those described in Sec-
tion 4.1.3 gave 11d (7.45 g, 87%) as a white solid after re-
crystallization of the concentration residue from C6H14/EtOAc. Mp:
132e134 ꢀC (from C6H14/EtOAc). IR (ATR): 3442, 3397, 3331, 3024,
1583, 1523, 1305, 1158, 1088, 469 cmꢁ1. 1H NMR (400 MHz, DMSO-
132 ꢀC (decomp.) (from C6H14/EtOAc). IR (ATR): 3467, 3034, 1742,
1402, 1339, 1249,1117, 1060, 983, 730, 694 cmꢁ1. 1H NMR (400 MHz,
CDCl3):
d
3.35 (6H, s), 5.26 (1H, d, J¼1.2 Hz), 5.35 (2H, s), 5.79 (2H, br
s), 6.93 (1H, d, J¼1.2 Hz), 7.40e7.43 (5H, m). 13C NMR (100 MHz,
CDCl3):
d 52.7, 69.3, 99.2, 109.0, 128.6, 128.8, 129.0, 134.2, 136.4,
d6):
d
4.38 (2H, dt, J¼4.9, 1.5 Hz), 5.10 (1H, dq, J¼10.6, 1.5 Hz), 5.21
150.50, 150.53. LRMS (EIþ) m/z: 291 [Mþ], 260, 216, 91. HRMS (EIþ)
m/z: calcd for C14H17N3O4 (Mþ) 291.1219, found 291.1194. Anal.
Calcd for C14H17N3O2: C, 57.72; H, 5.88; N, 14.43. Found: C, 57.59; H,
5.76; N, 14.23.
(1H, dq, J¼16.9, 1.5 Hz), 5.84e5.93 (1H, m), 6.86 (4H, br s). LRMS
(EIþ) m/z: 143 (Mþ), 86. HRMS (EIþ) m/z calcd for C5H9N3O2 (Mþ)
143.0695, found 143.0706.
4.1.7. N-Benzyloxycarbonylguanidine (11e). Similar treatments of
benzyl chloroformate (8.57 mL, 60 mmol) with guanidine mono-
hydrochloride (22.9 g, 240 mmol) to those described in Section
4.1.3 gave 11e (11.0 g, 95%) as a white solid after recrystallization of
the concentration residue from C6H14/EtOAc. Mp: 148e150 ꢀC
(from C6H14/EtOAc). IR (ATR): 3453, 3409, 3310, 3093, 1625, 1589,
4.1.12. tert-Butyl 2-amino-4-phenyl-1H-imidazol-1-carboxylate
(15). To a solution of 11a (239 mg, 1.5 mmol) in DMF (2.0 mL) was
added a solution of 14 (99.5 mg, 0.5 mmol) in DMF (1.0 mL). After
stirring at room temperature for 3 days, the solvent was removed in
vacuo. Separation of the residue by column chromatography (SiO2,
EtOAc) afforded 15 (28.3 mg, 22%) as a white solid and 16 (34.5 mg,
37%) as a pale yellow amorphous solid. Compound 15: mp:
134e136 ꢀC (from EtOAc). IR (KBr): 3463, 1740, 1637, 1342, 1121,
1523, 1295, 1149, 1069, 494 cmꢁ1 1H NMR (400 MHz, DMSO-d6):
.
d
4.94 (2H, s), 6.80 (4H, br s), 7.23e7.35 (5H, m). LRMS (EIþ) m/z: 193
(Mþ), 108, 91, 86. HRMS (EIþ) m/z calcd for C9H11N3O2 (Mþ)
1060 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d 1.59 (9H, s), 3.37 (6H, s),
193.0872, found 193.0872.
5.27 (1H, d, J¼1.2 Hz), 5.56 (2H, br s), 6.86 (1H, d, J¼1.2 Hz). 13C NMR
(100 MHz, CDCl3):
d 28.0, 52.7, 85.0, 99.4, 109.3, 135.6, 149.4, 150.6.
4.1.8. tert-Butyl 2-amino-4-dimethoxymethyl-1H-imidazol-1-carboxy-
late (13a). Table 1, run 2: to a solution of 11a (478 mg, 3.0 mmol) in
THF (3.0 mL) was added a solution of 8 (197 mg, 1.0 mmol) in THF
(2.0 mL). After heating at 50 ꢀC for 6 h, the solvent was removed in
vacuo. Purification of the residue by column chromatography (SiO2,
EtOAc) afforded 13a (159 mg, 62%) as a white solid. Mp: 134e136 ꢀC
(from EtOAc). IR (KBr): 3463, 1740, 1637, 1342, 1121, 1060 cmꢁ1. 1H
LRMS (EIþ) m/z: 257 [Mþ], 226, 125, 96. Anal. Calcd for C11H19N3O4:
C, 51.35; H, 7.44; N, 16.33. Found: C, 51.20; H, 7.33; N, 16.36. Com-
pound 16: IR (ATR): 3396, 2928, 1730, 1689, 1598, 1371, 1352, 1260,
1147, 1117, 758, 705, 688 cmꢁ1 1H NMR (400 MHz, CDCl3):
. d 1.67
(9H, s), 5.07 (2H, d, J¼2.3 Hz), 7.16 (1H, s), 7.37 (2H, t, J¼7.9 Hz), 7.57
(3H, t, J¼7.3 Hz), 7.63 (1H, t, J¼7.6 Hz), 7.77 (2H, d, J¼7.6 Hz), 8.08
(2H, d, J¼7.6 Hz). LRMS (EIþ) m/z: 377 [Mþ], 172. HRMS (ESIþ) m/z:
calcd for C22H24N3O3 (MþHþ) 378.18177, found 378.18258.
NMR (400 MHz, CDCl3):
d 1.59 (9H, s), 3.37 (6H, s), 5.27 (1H, d,
J¼1.2 Hz), 5.56 (2H, br s), 6.86 (1H, d, J¼1.2 Hz). 13C NMR (100 MHz,
CDCl3):
d
28.0, 52.7, 85.0, 99.4, 109.3, 135.6, 149.4, 150.6. LRMS (EIþ)
4.1.13. 2-Acetamido-4-phenyl-1H-imidazole (17). To a solution of 7
(303 mg, 3.0 mmol) in DMF (3.0 mL) was added 14 (199 mg,
1.0 mmol). After stirring at room temperature for 3 days, the sol-
vent was removed in vacuo. Purification of the residue by column
chromatography (SiO2, EtOAc) and further recrystallization from
MeOH afforded 17 (62.2 mg, 31%) as a light green solid. Mp:
229e231 ꢀC (from MeOH) (lit.8c mp: 230e231 ꢀC). 1H NMR
m/z: 257 [Mþ], 226, 125, 96. Anal. Calcd for C11H19N3O4: C, 51.35; H,
7.44; N, 16.33. Found: C, 51.20; H, 7.33; N, 16.36.
4.1.9. Methyl 2-amino-4-(dimethoxymethyl)-1H-imidazol-1-carboxy-
late (13b). Table 1, run 3: treatments of 8 (197 mg, 1.0 mmol) with
11b (351 mg, 3.0 mmol) in the same manner as described in Section
4.1.8 gave 13b (52.2 mg, 24%) as a yellow amorphous after purifi-
cation by column chromatography (SiO2, EtOAc). IR (ATR): 3459,
(400 MHz, DMSO-d6):
d
2.06 (3H, s), 7.15 (1H, t, J¼7.3 Hz), 7.24 (1H,
s), 7.31 (2H, t, J¼7.3 Hz), 7.69 (2H, d, J¼7.3 Hz). LRMS (EIþ) m/z: 201
3114, 1746, 1643, 1344, 1119, 1048, 981, 710 cmꢁ1
.
1H NMR
[Mþ], 159.
(400 MHz, CDCl3):
d
3.36 (6H, s), 3.45 (3H, s), 5.26 (1H, d, J¼0.9 Hz),
5.74 (2H, br s), 6.92 (1H, d, J¼0.9 Hz). The 1H NMR spectrum
showed that this sample was contaminated by a minute amount
(<ca. 5%) of the unidentified byproduct. 13C NMR (100 MHz, CDCl3):
4.1.14. tert-Butyl 5-(dimethoxymethyl)-1H-imidazol-2-ylcarbamate
(12a). To
a solution of 20a (100 mg, 0.47 mmol) in MeOH
(3.0 mL) were added trimethoxymethane (0.103 mL, 0.95 mmol)
and p-toluenesulfonic acid monohydrate (10 mg) under an argon
atmosphere, and the mixture was heated at reflux for 2 h. After
being cooled to room temperature, Et3N (0.05 mL) was added to
the mixture and the whole was concentrated in vacuo. Purifica-
d
52.7, 54.2, 99.2, 109.1, 136.4, 150.3, 151.1. LRMS (CIþ) m/z: 216
[MþHþ] 184. HRMS (CIþ) m/z: calcd for C8H14N3O4 (MþHþ)
216.0984, found 216.0975.
4.1.10. Allyl 2-amino-4-(dimethoxymethyl)-1H-imidazol-1-carboxy-
late (13d). Table 1, run 5: treatments of 8 (197 mg, 1.0 mmol) with
11d (429 mg, 3.0 mmol) in a manner similar to that described in
Section 4.1.8 gave 13d (57.7 mg, 24%) as a yellow oil after purifica-
tion by column chromatography (SiO2, EtOAc/CHCl3¼19/1). IR
tion of the residue by column chromatography (NHeSiO2, C6H14/
EtOAc¼1/1) afforded 12a (106 mg, 87%) as a colorless amorphous
solid. IR (KBr): 3272, 2979, 1717, 1621, 1287, 1254, 1165, 1070,
1046 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d 1.54 (9H, s), 3.34 (6H, s),
5.45 (1H, d, J¼0.6 Hz), 6.75 (1H, br s), 10.18 (1H, br s). 13C NMR
(ATR): 3457, 3109, 1749, 1638, 1331, 1178, 1111, 1051, 981, 693 cmꢁ1
.
(100 MHz, CDCl3): d 28.2, 52.3, 81.4, 98.0, 128.8, 137.9, 143.0,
1H NMR (400 MHz, CDCl3):
d
3.38 (6H, s), 4.83 (2H, td, J¼5.8,1.2 Hz),
153.1. LRMS (EIþ) m/z: 257 [Mþ], 226, 201, 170, 152, 111, 125, 96,
57. HRMS (EIþ) m/z: calcd for C13H19N3O4 (Mþ) 257.1376, found
257.1355.
5.28 (1H, d, J¼1.2 Hz), 5.37 (1H, qd, J¼10.4, 1.2 Hz), 5.44 (1H, qd,
J¼17.1, 1.2 Hz), 5.81 (2H, br s), 5.93e6.03 (1H, m), 6.95 (1H, d,
J¼1.2 Hz). 13C NMR (100 MHz, CDCl3):
d 52.7, 68.1, 99.2, 109.0, 120.1,
130.6, 136.4, 150.4, 150.5. LRMS (CIþ) m/z: 242 [MþHþ], 210. HRMS
4.1.15. tert-Butyl 4-phenyl-1H-imidazol-2-ylcarbamate (18). To
a solution of 15 (3.60 g, 14 mmol) and Boc2O (3.03 g, 14 mmol) in
THF (60 mL) was added sodium 1,1,1,3,3,3-hexamethyldisilazide
(NaHMDS) (1.0 mol/L solution in THF, 29 mL, 29 mmol) at room
temperature under an argon atmosphere, and the mixture was
stirred for 10 min. After saturated aqueous ammonium chloride
was added at 0 ꢀC, the mixture was extracted with EtOAc. The or-
ganic extracts were combined, washed with brine, dried over
(CIþ) m/z: calcd for C10H16N3O4 (MþHþ) 242.1141, found 242.1159.
4.1.11. Benzyl 2-amino-4-(dimethoxymethyl)-1H-imidazol-1-carboxy-
late (13e). Table 1, run 6: the same treatments of 8 (197 mg,
1.0 mmol) with 11e (580 mg, 3.0 mmol) as those described in Sec-
tion 4.1.8 gave 13e (108 mg, 37%) as a pale yellow solid after puri-
fication by column chromatography (SiO2, EtOAc/CHCl3¼19/1). Mp: