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E. Diamanti et al. / Bioorg. Med. Chem. 20 (2012) 2082–2090
was transformed into the oxalate salt, which was recrystallized
from EtOH: mp 89–91 °C. Anal. Calcd for C12H16N2O2ÁC2H2O4: C,
54.19; H, 5.85; N, 9.03. Found: C, 54.44; H, 5.99; N, 9.24.
3.78 (s, 3, OCH3), 4.79 (q, 1, CHCH3), 6.79 (d, 1, ArH), 6.93 (t, 1, ArH),
7.20 (t, 1, ArH), 7.58 (d, 1, ArH). Anal. Calcd for C10H11BrO3: C,
46.36; H, 4.28. Found: C, 46.49; H, 4.15.
5.1.10. 2-(1-(2-(Methylsulfonyl)phenoxy)ethyl)-4,5-dihydro-1H-
imidazole (20)
5.1.16. Methyl 2-(2-(trifluoromethyl)phenoxy)propanoate (30)
This was prepared as described for 28 starting from 2-tri-
fluoromethyl-phenol (Aldrich) (82% yield). 1H NMR (CDCl3) d
1.64 (d, 3, CH3CH), 3.77 (s, 3, OCH3), 4.81 (q, 1, CHCH3), 6.81
(d, 1, ArH), 7.02 (t, 1, ArH), 7.41 (t, 1, ArH), 7.60 (d, 1, ArH).
Anal. Calcd for C11H11F3O3: C, 53.23; H, 4.47. Found: C, 53.48;
H, 4.33.
This was prepared as described for 2 starting from 39 (49%
yield): mp 143–145 °C. 1H NMR (CDCl3) d 1.68 (d, 3, CH3CH), 3.21
(s, 3, SO2CH3), 3.39–3.62 (m, 4, NCH2CH2N), 5.36 (q, 1, CHCH3),
7.14 (m, 2, ArH), 7.58 (t, 1, ArH), 7.93 (d, 1, ArH), 8.16 (br s, 1,
NH, exchangeable with D2O). The free base was transformed into
the oxalate salt, which was recrystallized from EtOH: mp 107–
109 °C. Anal. Calcd for C12H16N2O3SÁC2H2O4: C, 46.92; H, 5.06; N,
7.82; S, 8.95. Found: C, 46.70; H, 5.23; N, 7.59; S, 9.12.
5.1.17. Methyl 2-(2-(prop-1-en-2-yl)phenoxy)propanoate (31)
This was prepared as described for 28 starting from 2-(prop-1-
en-2-yl)phenol20 (77% yield). 1H NMR (CDCl3) d 1.61 (d, 3, CH3CH),
2.18 (s, 3, CH3C@CH2), 3.76 (s, 3, OCH3), 4.79 (q, 1, CHCH3), 5.12 (d,
1, CH2=CCH3), 5.18 (d, 1, CH2=CCH3), 6.76 (d, 1, ArH), 6.94 (t, 1,
ArH), 7.18 (t, 1, ArH), 7.22 (d, 1, ArH). Anal. Calcd for C13H16O3: C,
70.89; H, 7.32. Found: C, 70.68; H, 7.46.
5.1.11. 2-(1-(4,5-Dihydro-1H-imidazol-2-
yl)ethoxy)benzaldehyde (21)
A mixture of 4111 (0.35 g, 1.33 mmol) and HCl 2 N (20 mL) was
stirred at 25 °C for 2 h. The solution was basified with NaOH 2 N
and extracted with CHCl3. Removal of dried solvents afforded a res-
idue which was purified by flash chromatography using cyclohex-
ane/AcOEt/MeOH/33%NH4OH (6:4:1:0.1) to give a colorless oil:
0.24 g (84% yield). 1H NMR (CDCl3) d 1.65 (d, 3, CH3CH), 3.42–
3.68 (m, 4, NCH2CH2N), 4.63 (q, 1, CHCH3), 6.94–7.52 (m, 4, ArH),
8.03 (br s, 1, NH, exchangeable with D2O), 10.40 (s, 1, CHO). The
free base was transformed into the dibenzoyl tartrate salt, which
was recrystallized from 2-PrOH: mp 138–141 °C. Anal. Calcd for
5.1.18. Methyl 2-(2-(cyclopropylmethyl)phenoxy)propanoate
(32)
This was prepared as described for 28 starting from 2-(cyclo-
propylmethyl)phenol21 (68% yield). 1H NMR (CDCl3) d 0.20 (m, 2,
cyclopropyl), 0.52 (m, 2, cyclopropyl), 1.03 (m, 1, cyclopropyl),
1.64 (d, 3, CH3CH), 2.61 (d, 2, CH2), 3.78 (s, 3, OCH3), 4.79 (q, 1,
CHCH3), 6.64 (d, 1, ArH), 6.93 (t, 1, ArH), 7.16 (t, 1, ArH), 7.31 (d,
1, ArH). Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C,
71.56; H, 7.53.
C
12H14N2O2ÁC18H14O8: C, 62.50; H, 4.90; N, 4.86. Found: C, 62.77;
H, 5.04; N, 4.74.
5.1.12. 1-(2-(1-(4,5-Dihydro-1H-imidazol-2-
yl)ethoxy)phenyl)ethanone (22)
5.1.19. Methyl 2-(2-ethoxyphenoxy)propanoate (33)
This was prepared as described for 28 starting from 2-ethoxy-
phenol (Aldrich) (82% yield). 1H NMR (CDCl3) d 1.40 (t, 3, CH3CH2),
1.61 (d, 3, CH3CH), 3.77 (s, 3, OCH3), 4.14 (q, 2, CH2CH3), 4.78 (q, 1,
CHCH3), 6.81–7.03 (m, 4, ArH). Anal. Calcd for C12H16O4: C, 64.27;
H, 7.19. Found: C, 64.52; H, 7.41.
This was prepared as described for 2 starting from 40 (62% yield).
1H NMR (CDCl3) d 1.66 (d, 3, CH3CH), 2.62 (s, 3, COCH3), 3.44–3.72 (m,
4, NCH2CH2N), 5.17 (q, 1, CHCH3), 7.04 (m, 2, ArH), 7.42 (t, 1, ArH),
7.68 (d, 1, ArH), 7.93 (br s, 1, NH, exchangeable with D2O). The free
base was transformed into the oxalate salt, which was recrystallized
from EtOH: mp 120–122 °C. Anal. Calcd for C13H16N2O2ÁC2H2O4: C,
55.90; H, 5.63; N, 8.69. Found: C, 55.69; H, 5.91; N, 8.53.
5.1.20. Methyl 2-(2-cyclopropoxyphenoxy)propanoate (34)
This was prepared as described for 28 starting from 2-cyclo-
propoxyphenol22 (74% yield). 1H NMR (CDCl3) d 0.81 (m, 4, cyclo-
propyl), 1.63 (d, 3, CH3CH), 3.78 (s, 3, OCH3), 3.80 (m, 1,
cyclopropyl), 4.71 (q, 1, CHCH3), 6.93 (m, 2, ArH), 7.01 (m, 1,
ArH), 7.23 (d, 1, ArH). Anal. Calcd for C13H16O4: C, 66.09; H, 6.83.
Found: C, 66.18; H, 6.65.
5.1.13. 2-(1-(2,6-Diphenylphenoxy)ethyl)-4,5-dihydro-1H-
imidazole (27)
This was prepared as described for 2 starting from 42 (56%
yield). 1H NMR (CDCl3) d 0.93 (d, 3, CH3CH), 2.91–3.37 (m, 4,
NCH2CH2N), 4.19 (q, 1, CHCH3), 7.20–7.61 (m, 13, ArH), 7.90 (br s,
1, NH, exchangeable with D2O). The free base was transformed into
the oxalate salt, which was recrystallized from EtOH: mp 136–
137 °C. Anal. Calcd for C23H22N2OÁC2H2O4: C, 69.43; H, 5.59; N,
6.48. Found: C, 69.23; H, 5.78; N, 6.23.
5.1.21. Methyl 2-(2-(vinyloxy)phenoxy)propanoate (35)
This was prepared as described for 28 starting from 2-(vinyl-
oxy)phenol23 (77% yield). 1H NMR (CDCl3) d 1.65 (d, 3, CH3CH),
3.75 (s, 3, OCH3), 4.40 (d, 1, CH2=CH), 4.75 (d, 1, CH2=CH), 4.78
(q, 1, CHCH3), 6.61 (dd, 1, CH@CH2), 6.89–7.12 (m, 4, ArH). Anal.
Calcd for C12H14O4: C, 64.85; H, 6.35. Found: C, 64.98; H, 6.52.
5.1.14. Methyl 2-(2-chlorophenoxy)propanoate (28)
A mixture of 2-chloro-phenol (Aldrich) (1.50 g, 11.6 mmol),
methyl 2-bromopropionate (1.74 g, 11.6 mmol), and K2CO3
(1.60 g, 11.6 mmol) in DME was refluxed for 18 h. The mixture
was cooled and filtered. The solvent was removed under reduced
pressure to give a residue, which was taken up in CH2Cl2 and
washed with cold 2 N NaOH. Removal of solvent afforded an oil
which was purified by flash chromatography eluting with cyclo-
hexane/EtOAc (95:5): 2.23 g (90% yield). 1H NMR (CDCl3) d 1.70
(d, 3, CH3CH), 3.78 (s, 3, OCH3), 4.80 (q, 1, CHCH3), 6.82 (d, 1,
ArH), 6.95 (t, 1, ArH), 7.19 (t, 1, ArH), 7.39 (d, 1, ArH). Anal. Calcd
for C10H11ClO3: C, 55.96; H, 5.17. Found: C, 55.78; H, 5.27.
5.1.22. Methyl 2-(2-methoxyphenoxy)propanoate (36)
This was prepared as described for 28 starting from 2-methoxy-
phenol (Aldrich) (90% yield). 1H NMR (CDCl3) d 1.62 (d, 3, CH3CH),
3.77 (s, 3, OCH3), 3.89 (s, 3, ArOCH3), 4.81 (q, 1, CHCH3), 6.86–7.06
(m, 4, ArH). Anal. Calcd for C11H14O4: C, 62.85; H, 6.71. Found: C,
62.66; H, 6.58.
5.1.23. Methyl 2-(2-(methylthio)phenoxy)propanoate (37)
This was prepared as described for 28 starting from 2-(methyl-
thio)-phenol (Aldrich). White solid (82% yield): mp 50–51 °C. 1H
NMR (CDCl3) d 1.75 (d, 3, CH3CH), 2.45 (s, 3, SCH3), 3.80 (s, 3,
OCH3), 4.80 (q, 1, CHCH3), 6.78 (d, 1, ArH), 7.00 (t, 1, ArH), 7.18
(t, 1 ArH), 7.20 (d, 1, ArH). Anal. Calcd for C11H14O3S: C, 58.38; H,
6.24; S, 14.17. Found: C, 58.58; H, 6.03; S, 14.00.
5.1.15. Methyl 2-(2-bromophenoxy)propanoate (29)
This was prepared as described for 28 starting from 2-bromo-
phenol (Aldrich) (88% yield). 1H NMR (CDCl3) d 1.71 (d, 3, CH3CH),