F. Daryaee et al. / European Journal of Medicinal Chemistry 44 (2009) 289e295
293
1
amide). H NMR (CDCl ): d 4.14 (s, 2H, glycolyl CH ), 3.76
Anal. Calcd for C H NO : C, 40.33; H, 7.62; N, 11.76%.
4
9
3
3
2
Found: C, 40.18; H, 7.65; N, 11.79%.
(s, 1H, OH), 3.61 (t, 2H, CH , J ¼ 5.4 Hz), 3.20 (t, 2H, CH ,
2
2
J ¼ 5.4 Hz), 1.68 (m, 2H, CH ), 1.59 (m, 4H, CH ). MS (EI)
2
2
ꢃ
þ
6
.4. Synthesis of N-glycolyl-2-amino-1-butanol (3b)
m/z (%): 143.3 (M , 59), 112.2 (100). Anal. Calcd for
C H NO : C, 58.72; H, 9.15; N, 9.78%. Found: C, 58.50;
H, 8.95; N, 10.13%.
7
13
2
The title compound was prepared by the reaction between 1
(
1
116 mg, 1 mmol) and 2-amino-1-butanol (2a, 89 mg,
mmol) as described for compound 3a. The crude solid thus
obtained was crystallized from ethylacetate, to give 59 mg
6.8. Synthesis of 4-glycolyl-morpholine (3f)
ꢁ
ꢀ1
of 3b, in a 40% yield. Mp: 80e82 C. IR (cm ): 3380
1
(
This compound was prepared by the reaction between 1
(116 mg, 1 mmol) and morpholine (2f, 87 mg, 1 mmol) as de-
scribed for compound 3a. After evaporation of the solvent un-
der reduced pressure, the residue was crystallized from
ethylacetate to give 44 mg of 3f, in a 30% yield. Mp: 80e
NH, amide), 3280 (OH, alcohol), 1620 (CO, amide).
H
NMR (DMSO-d ): d 7.28 (d, 1H, amide NH, J ¼ 8 Hz), 5.50
6
(
s, 1H, OH), 4.54 (s, 1H, OH), 3.79 (s, 2H, glycolyl CH ),
2
3
1
.65 (m, 2H, CH ), 3.35 (m, 1H, CH), 1.59 (m, 1H, CH),
2
ꢁ
ꢁ
ꢀ1
.36 (m, 1H, CH), 0.82 (t, 3H, CH , J ¼ 7.2 Hz). MS (EI)
83 C (lit. [11]: 80e82 C). IR (cm ): 3420 (OH, alcohol),
3
ꢃ
þ
1
1650 (CO, amide). H NMR (CDCl ): d 4.17 (s, 2H, glycolyl
m/z (%): 147.2 (M , 30), 116.1 (100). Anal. Calcd for
C H NO : C, 48.97; H, 8.90; N, 9.52%. Found: C, 49.07;
H, 8.93; N, 9.55%.
3
CH ), 3.70 (m, 6H, CH ), 3.62 (s, 1H, OH), 3.29 (t, 2H, CH ,
2
6
13
3
2
2
ꢃ
þ
J ¼ 4.8 Hz). MS (EI) m/z (%): 145.2 (M , 34), 114.2 (100).
Anal. Calcd for C H NO : C, 49.65; H, 7.64; N, 9.65%.
3
6
11
6
.5. Synthesis of N-glycolyl-diethanolamine (3c)
Found: C, 49.78; H, 7.84; N, 9.34%.
This compound was prepared by the reaction between 1
116 mg, 1 mmol) and diethanolamine (2c, 105 mg, 1 mmol)
6.9. Synthesis of 1,4-diglycolyl-piperazine (3g)
(
as described for compound 3a. The crude oily product was pu-
rified by column chromatography (methanol) to give 24.5 mg
The title compound was prepared by the reaction between 1
(232 mg, 2 mmol) and piperazine (2g, 86 mg, 1 mmol) as de-
scribed for compound 3a. After evaporation of organic solvent
under reduced pressure, the residue was crystallized from
methanol to give 40 mg of 3g, in a 20% yield. Mp: 194e
ꢀ
1
of 3c as a pure oily compound in a 15% yield. IR (cm ):
1
200e3520 (OH, alcohol), 1640 (CO, amide). H NMR
3
(
DMSO-d ): d 4.80 (s, 2H, OH), 4.30 (s, 1H, OH), 4.12 (s,
6
ꢁ
ꢁ
ꢀ1
2
H, glycolyl CH ), 3.53 (m, 4H, CH ), 3.36 (t, 2H, CH ,
2
197 C (lit. [12]: 187e190 C). IR (cm ): 3240e3400 (OH,
2
2
1
alcohol), 1640 (CO, amide). H NMR (DMSO-d ): d 4.67 (t,
J ¼ 5.6 Hz), 3.26 (t, 2H, CH , J ¼ 5.6 Hz). MS (EI) m/z (%):
2
6
þ
1
63.2 (M , 45), 120.1 (100). Anal. Calcd for C H NO : C,
6
2H, OH, J ¼ 5.6 Hz), 4.10 (d, 4H, glycolyl CH , J ¼ 5.6 Hz),
13
4
2
þ
4
4.16; H, 8.03; N, 8.58%. Found: C, 44.43; H, 7.95; N, 8.25%.
3.48 (m, 8H, CH ). MS (EI) m/z (%): 202.3 (M , 5), 113.2
2
(100). Anal. Calcd for C H N O : C, 47.52; H, 6.98; N,
13.85. Found: C, 47.12; H, 7.01; N, 13.98.
8 14 2 4
6
.6. Synthesis of 1-glycolyl-pyrrolidine (3d)
This compound was prepared by the reaction between 1
116 mg, 1 mmol) and pyrrolidine (2d, 71 mg, 1 mmol) as de-
6.10. Synthesis of N-glycolyl-2-phenyl-ethylamine (3h)
(
scribed for compound 3a. The crude product was purified by col-
This compound was prepared by the reaction between 1
(116 mg, 1 mmol) and 2-pheny-ethylamine (2h, 121 mg,
1 mmol) as described for compound 3a. The crude product
was purified by column chromatography on silica gel (chloro-
umn chromatography on silica gel (hexane/chloroform, 7:3, 1:1,
ꢁ
chloroform) to give 26 mg of 3d, in a 20% yield. Mp: 40 C (lit.
ꢀ1
ꢁ
[
(
11]: 42e44 C). IR (cm ): 3200e3480 (OH, alcohol), 1640
1
CO, amide). H NMR (CDCl ): d 4.08 (s, 2H, glycolyl CH ),
ꢁ
form) to give 18 mg of 3h, in a 10% yield. Mp: 71e73 C (lit.
ꢀ1
3
2
ꢁ
3
.59 (s, 1H, OH), 3.54 (t, 2H, CH , J ¼ 6.4 Hz), 3.29 (t, 2H,
[13]: 74e75 C). IR (cm ): 3360 (NH, amide), 3160 (OH, al-
2
1
cohol), 1640 (CO, amide), 1550, 1470 (CeC, aromatic). H
CH , J ¼ 6.8 Hz), 1.99 (qu, 2H, CH , J ¼ 6.4 Hz), 1.90 (qu,
2
2
ꢃ
þ
2
H, CH , J ¼ 6.8 Hz). MS (EI) m/z (%): 129.2 (M , 37), 98.2
NMR (CDCl ): d 7.26 (m, 5H, AreH), 6.56 (s, 1H, OH),
3
2
(
100). Anal. Calcd for C H NO : C, 55.80; H, 8.58; N,
2
4.06 (s, 2H, CH ), 3.57 (q, 2H, CH , J ¼ 6 Hz), 2.84 (t, 2H,
6
11
2
2
ꢃ
þ
1
0.84%. Found: C, 55.45; H, 8.83; N, 10.64%.
CH , J ¼ 6 Hz). MS (EI) m/z (%): 179.3 (M , 21), 104.2
2
(100). Anal. Calcd for C H NO : C, 67.02; H, 7.31; N,
7.82%. Found: C, 67.27; H, 7.41; N, 7.65%.
10 13 2
6
.7. Synthesis of 1-glycolyl-piperidine (3e)
The title compound was prepared by the reaction between 1
116 mg, 1 mmol) and piperidine (2e, 85 mg, 1 mmol) as
6.11. Synthesis of 2-glycolylamino-2-methyl-1,
3-propanediol (3i)
(
described for compound 3a. The final solution was washed
with hydrochloric acid (3 M, 5 mL), the organic layer was sep-
arated and the solvent was evaporated under reduced pressure
This compound was prepared by the reaction between 1
(116 mg, 1 mmol) and 2-amino-2-methyl-1,3-propanediol
(2i, 133 mg, 1 mmol) as described for compound 3a. The sol-
vent was removed under vacuum to give 182 mg of 3i, in
ꢁ
to give 43 mg of 3e, in a 30% yield. Mp: 39e40 C (lit. [11]:
ꢀ1
ꢁ
3
9e41 C). IR (cm ): 3400e3440 (OH, alcohol), 1650 (CO,