R. Di Santo et al. / Bioorg. Med. Chem. 10 (2002) 2511–2526
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1
14. IR: n 1680 (CO) cmꢀ1; H NMR: d 1.39 (t, 3H,
J=7.0 Hz, CH3), 2.47 (dd, 1H, Jgem=4.7 Hz, Jvic1=2.5
Hz, oxyrane CHH), 2.83 (dd, 1H, Jgem=4.7 Hz,
Jvic2=4.5 Hz, oxyrane CHH), 3.40 (m, 1H, CH), 4.25–
4.37 (m, 3H, CHH–pyrrole and CH2CH3), 4.83 (dd, 1H,
Jgem=14.7 Hz, Jvic3=5.6 Hz, CHH–pyrrole), 6.19 (dd,
1H, J3,4=4.0 Hz, J4,5=2.6 Hz, pyrrole C4-H), 6.92–7.03
(m, 2H, pyrrole C3-H and C5-H); anal. C10H13NO3
(195.22) C, H, N.
2d. IR: n 3400 (NH and OH), 1680 (CO) cmꢀ1
;
1H
NMR: d 1.23 (t, 3H, J=7.1Hz, CH ), 2.65 (bs, 1H,
3
OH), 3.08–3.35 (m, 2H, CH2NH), 3.90–4.24 (m, 5H,
CH2–pyrrole, CH2CH3, and CH), 4.60 (bs, 1H, NH),
6.62–7.49 (m, 11H, pyrrole and benzene H); anal.
C22H22ClN2O3 (398.89) C, H, Cl, N.
2e. IR: n 3380 (NH and OH), 1670 (CO) cmꢀ1 1H
;
NMR: d 1.23 (t, 3H, J=7.1Hz, CH ), 2.66 (bs, 1H,
3
OH), 3.05 (dd, 1H, Jgem=12.8 Hz, Jvic1=7.1Hz,
CHHNH), 3.23 (dd, 1H, Jgem=12.8 Hz, Jvic2=3.7 Hz,
CHHNH), 3.88–4.24 (m, 6H, CH2–pyrrole, CH2CH3,
CH and NH), 6.45–7.48 (m, 11H, pyrrole and benzene
H); anal. C22H22ClN2O3 (398.89) C, H, Cl, N.
Ethyl 1-[3-(2-methyl)phenylamino-2-hydroxypropyl]-4-
phenyl-1H-pyrrole-3-carboxylate (2a). A mixture of 11
(500 mg, 1.9 mmol) and 2-methylaniline (200 mg, 1.9
mmol) were heated at 90 ꢁC for 5 h. The cooled mixture
was dissolved in chloroform and chromatographed on
silica gel column (chloroform as eluent) to obtain pure
2a (490 mg, 68% yield): IR: n 3400 (NH and OH), 1680
2f. IR: n 3400, 3370, 3220, 3100 (NH2, NH and OH),
1
1670 (CO) cmꢀ1; H NMR: d 1.23 (t, 3H, J=7.1Hz,
(CO) cmꢀ1
;
1H NMR: d 1.26 (t, 3H, J=7.0 Hz,
CH3), 3.06 (dd, 1H, Jgem=12.8 Hz, Jvic1=7.6 Hz,
CHHNH), 3.26 (dd, 1H, Jgem=12.8 Hz, Jvic2=3.7 Hz,
CHHNH), 3.35 (bs, 4H, NH2, NH and OH), 3.90–4.25
(m, 5H, CH2–pyrrole, CH2CH3, and CH), 6.61–6.86 (m,
5H, pyrrole C5-H and aniline H), 7.26–7.50 (m, 6H,
pyrrole C2-H and benzene H); anal. C22H25N3O3
(379.46) C, H, N.
CH2CH3), 2.16 (s, 3H, CH3), 2.55 (bs, 1H, OH), 3.16
(dd, 1H, Jgem=13.0 Hz, Jvic1=7.3 Hz, CHHNH), 3.33
(dd, 1H, Jgem=13.0 Hz, Jvic2=3.9 Hz, CHHNH), 3.80–
4.25 (m, 6H, CH2–pyrrole, CH2CH3, CH and NH),
6.58–7.50 (m, 11H, pyrrole and benzene H); anal.
C23H26N2O3 (378.47) C, H, N.
The cited reaction was used to obtain propanolamines
1a, 1d, 2b–h, 2j–m, while arylthiopropanoles 2n–o were
obtained with the same procedure using ethanol as a
solvent and refluxing the mixture for 6 h. Spectroscopic
data of these derivatives are reported below:
2g. IR: n 3400, 3340, 3100 (NH2, NH and OH), 1670
1
(CO) cmꢀ1; H NMR: d 1.23 (t, 3H, J=7.1Hz, CH ),
3
2.98 (dd, 1H, Jgem=12.6 Hz, Jvic1=7.2 Hz, CHHNH),
3.19 (dd, 1H, Jgem=12.6 Hz, Jvic2=3.5 Hz, CHHNH),
3.20 (bs, 4H, NH2, NH and OH), 3.85–4.25 (m, 5H,
CH2–pyrrole, CH2CH3, and CH), 6.55 (m, 4H, aniline
H), 6.69 (d, 1H, J2,5=2.3 Hz, pyrrole C5-H), 7.21–7.50
(m, 6H, pyrrole C2-H and benzene H); anal.
C22H25N3O3 (379.46) C, H, N.
1a. IR: n 3480, 3340 (NH and OH), 1680 (CO) cmꢀ1; 1H
NMR: d 1.40 (t, 3H, J1=7.2 Hz, CH2CH3), 3.07 (d, 1H,
J2=4.2 Hz, OH), 3.37 (m, 2H, CH2NH), 3.85 (s, 3H,
OCH3), 4.31–4.41 (m, 3H, CH2CH3 and CH), 4.67 (m,
2H, CH2–indole), 6.56–7.93 (m, 12H, indole and ben-
zene H), 8.03 (bs, 1H, NH); anal. C22H24N2O5 (396.44)
C, H, N.
2h. IR: n 3420, 3350 (NH and OH), 1670 (CO) cmꢀ1; 1H
NMR: d 1.23 (t, 3H, J=7.1Hz, CH CH3), 1.60 and
2
2.39 (2bs, 2H, NH and OH), 3.31(m, 2H, C H2NH),
3.86 (s, 3H, OCH3), 4.02 (m, 2H, CH2–pyrrole), 4.14–
4.24 (m, 3H, CH2CH3 and CH), 6.62–6.72 (m, 3H, pyr-
role C5-H and anthranilate C3-H and C5-H), 7.21–7.50
(m, 7H, pyrrole C2-H, anthranilate C4-H and benzene
H), 7.93 (m, 1H, anthranilate C6-H); anal. C24H26N2O5
(422.48) C, H, N.
1d. IR: n 3490, 3340 (NH and OH), 1680 (CO) cmꢀ1; 1H
NMR: d 1.40 (t, 3H, J=7.0 Hz, CH2CH3), 2.95 (bs, 1H,
OH), 3.36 (m, 2H, CH2NH), 3.85 (s, 3H, OCH3), 4.32–
4.42 (m, 3H, CH2CH3 and CH), 4.70 (m, 2H, CH2-
indole), 6.59–6.71(m, 2H, anthranilate C3-H and C5-
H), 7.21–7.93 (m, 6H, indole and benzene H), 8.03 (bs,
1H, NH); anal. C22H23ClN2O3 (430.89) C, H, Cl, N.
2j. IR: n 3380 (NH and OH), 1685 (CO) cmꢀ1 1H
;
NMR: d 1.22 (t, 3H, J1=7.2 Hz, CH2CH3), 2.79 (d,
1H, J2=4.2 Hz, OH), 3.14–3.31 (m, 2H, CH2NH),
3.85 (s, 3H, OCH3), 3.90–4.10 (m, 3H, CH2–pyrrole
and CH), 4.18 (q, 2H, J1=7.2 Hz, CH2CH3), 4.50
(bs, 1H, NH), 6.56 (m, 2H, aniline C2-H and C6-H),
6.69 (d, 1H, J2,5=2.5 Hz, pyrrole C5-H), 7.25–7.48
(m, 6H, pyrrole C2-H and benzene H), 7.85 (m, 2H,
aniline C3-H and C5-H); anal. C24H26N2O5 (422.48) C,
H, N.
2b. IR: n 3380 (NH and OH), 1680 (CO) cmꢀ1 1H
;
NMR: d 1.22 (t, 3H, J=7.0 Hz, CH2CH3), 2.27 (s, 3H,
CH3), 2.80 (bs, 1H, OH), 3.05 (dd, 1H, Jgem=13.0 Hz,
Jvic1=7.2 Hz, CHHNH), 3.24 (dd, 1H, Jgem=13.0 Hz,
Jvic2=3.8 Hz, CHHNH), 3.83–4.23 (m, 6H, CH2–pyr-
role, CH2CH3, CH and NH), 6.41–7.49 (m, 11H, pyr-
role and benzene H); anal. C23H26N2O3 (378.47) C, H,
N.
2c. IR: n 3440, 3380 (NH and OH), 1670 (CO) cmꢀ1; 1H
NMR: d 1.22 (t, 3H, J=7.2 Hz, CH2CH3), 2.24 (s, 3H,
CH3), 2.60 (bs, 1H, OH), 3.05 (dd, 1H, Jgem=13.0 Hz,
Jvic1=7.4 Hz, CHHNH), 3.25 (dd, 1H, Jgem=13.0 Hz,
Jvic2=3.7 Hz, CHHNH), 3.70–4.24 (m, 6H, CH2–pyrrole,
CH2CH3, CH and NH), 6.49–7.77 (m, 11H, pyrrole and
benzene H); anal. C23H26N2O3 (378.47) C, H, N.
2k. IR: n 3280 (NH and OH), 1665 (CO) cmꢀ1 1H
;
NMR: d 1.29 (t, 3H, J=7.0 Hz, CH3), 2.50 (bs, 1H,
OH), 3.20 (dd, 1H, Jgem=13.2 Hz, Jvic1=7.2 Hz,
CHHNH), 3.31(dd, 1H, Jgem=13.2 Hz, Jvic2=4.0 Hz,
CHHNH), 3.95–4.29 (m, 6H, CH2–pyrrole, CH2CH3,
CH and NH), 6.66–7.47 (m, 11H, pyrrole and benzene
H); anal. C22H23ClN2O3 (398.89) C, H, Cl, N.