P. B. S. Dawadi et al.
[3-13C]-5-cyano-3-(methoxycarbonylethyl)-4-(methoxycar-
bonylmethyl)-pyrrole (7b)
the residue was dissolved in H2O and EtOAc. The mixture was
extracted with EtOAc (2 ꢁ 100 mL). The organic solution was
washed with H2O and saturated NaCl and dried over MgSO4. The
solution was filtered and the solvent was evaporated. The
product was purified by column chromatography (silicagel 60:
ethyl acetate/n-hexane, 1:1) to yield 5-cyano-4-(methoxycarbo-
nylethyl)-3-(hydroxyethyl)-pyrrole as a colorless solid (1.51 g,
Similarly, [3-13C]-5-cyano-3-(methoxycarbonylethyl)-4-(tetrahydrop-
yran-20-yloxyethyl)-pyrrole 6b (2.45 g, 8 mmol) yielded 5-cyano-4-
(methoxycarbonylethyl) - 3 - (hydroxyethyl) - pyrrole (1.35 g, 76%).
1H-NMR (300 MHz, acetone-d6): d= 2.58–2.62 (m, 2H), 2.76–2.80
3
3
85%). 1H-NMR (300 MHz, acetone-d6): d = 2.58 (t, JH;H = 7.5 Hz,
3
(m, 2H), 2.80 (dt, JH;H =7.2Hz, JH,C =4.3Hz, 2H), 3.62 (s, OCH3),
3
3
3
3
3
3.70 (bdt, JH;H =7.2Hz, JH;H =5.6Hz, 2H), 3.86 (bt, JH;H =5.6Hz,
2
1H), 6.90 (dd, JH,C =7.1Hz, JH;H = 2.9Hz, 1H), 10.89 (bs, NH) ppm.
2H), 2.76 (t, JH;H = 7.3 Hz, 2H), 2.80 (t, JH;H = 7.2 Hz, 2H), 3.62
3
3
3
(s, OCH3), 3.70 (dt, JH;H = 7.2 Hz, JH;H = 5.6 Hz, 2H), 3.88 (bt,
3JH;H = 7.2 Hz, 1H), 6.90 (d, 3JH;H = 2.9 Hz, 1H), 10.87 (bs, NH) ppm.
13C-NMR (75 MHz, acetone-d6): d = 20.8, 29.3, 35.2, 51.6 (OCH3),
62.8, 100.5 (C-5), 114.9 (CN), 122.5 (C-2), 123.5 (C-3), 131.2 (C-4),
173.6 (C = O) ppm.
13C-NMR (75 MHz, acetone-d6): d =20.8 (d, JC,C = 49Hz, CH2), 29.3
1
(d, 2JC,C =2.0Hz, CH2), 35.2 (d, 2JC,C =1.5Hz, CH2), 51.6 (OCH3), 62.8
3
2
(d, JC,C =1.0Hz, CH2), 100.5 (d, JC,C = 6.7 Hz, C-5), 114.9 (d,
3JC,C = 4.9 Hz, CN), 122.5 (d, JC,C = 73 Hz, C-2), 123.5 (13C-labeled,
1
1
intense peak, C-3), 131.2 (d, JC,C =54Hz, C-4), 173.6 (d,
To a cold solution (01C) of 5-cyano-4-(methoxycarbonylethyl)-
3-(hydroxyethyl)-pyrrole (1.51 g, 7 mmol) in acetone (100 mL)
was added Jones reagent (2.6 M, 4 mL, 10 mmol) dropwise
over the period of 90 min. To the reaction mixture was
added isopropanol (20 mL) and stirred for 30 min at room
temperature. The mixture was filtered through celite and
washed with acetone (100 mL). The crude acid was dissolved
in ether/ethyl acetate mixture (10 mL, 1:1) and treated with
ethereal diazomethane at 01C. The mixture was stirred for 2 h,
solvent evaporated and the residue was purified by column
chromatography (silicagel 60: ethyl acetate/n-hexane, 1:3) to
yield 5 - cyano-3-(methoxycarbonylethyl)-4-(methoxycarbonyl-
methyl)-pyrrole 7 as a light-yellow oil (0.51 g, 30%). 1H-NMR
(300 MHz, CDCl3): d = 2.58 (t, 3JH;H = 7.3 Hz, 2H), 2.74
3JC,C =3.8Hz, C=O)ppm. HRMS calculated for 13C1C10H14N2O3,
[M]1: 223.1038; found: 223.1023.
Similarly, 5-cyano-4-(methoxycarbonylethyl)-3-(hydroxyethyl)-
pyrrole (1.35 g, 6 mmol) afforded 7b (0.48 g, 32%). 1H-NMR
3
3
(300 MHz, CDCl3): d = 2.58 (bdt, JH;H = 7.4 Hz, JH,C = 4.4 Hz, 2H),
2
3
2.74 (bdt, JH,C = 7.2 Hz , 3JH;H = 7.2 Hz, 2H), 3.63 (d, JH,C = 4.2 Hz,
2
2H), 3.67 (s, OCH3), 3.73 (s, OCH3), 6.72 (dd, JH,C = 6.8 Hz,
3JH;H = 3.0 Hz, 1H), 8.76 (bs, NH) ppm. 13C-NMR (75 MHz, CDCl3):
1
2
d = 20.8 (d, JC,C = 49 Hz, CH2), 30.2 (d, JC,C = 2.0 Hz, CH2), 34.2
(d, JC,C = 1.6 Hz, CH2), 51.7 (OCH3), 52.2 (OCH3), 100.7 (d,
2
2JC,C = 1.9 Hz, C-5), 113.8 (d, JC,C = 4.8 Hz, CN), 121.8 (d,
3
1JC,C = 80 Hz, C-2), 122.8 (13C-labeled, intense peak, C-3), 125.6
1
3
(d, JC,C = 56 Hz, C-4), 171.1 (d, JC,C = 1.3 Hz, C = O), 173.5 (d,
3JC,C = 3.5 Hz, C = O) ppm. HRMS calculated for 13C1C11H14N2O4,
[M]1: 251.0987; found: 251.0963.
3
(t, JH;H = 7.3 Hz, 2H), 3.63 (s, 2H), 3.67 (s, OCH3), 3.73 (s, OCH3),
6.72 (d, JH;H = 3.0 Hz, 1H), 9.64 (bs, NH) ppm. 13C-NMR (75 MHz,
3
CDCl3): d = 20.0, 30.2, 34.3, 51.7 (OCH3), 52.2 (OCH3), 100.7 (C-5),
113.8 (CN), 121.8 (C-2), 122.8 (C-3), 125.6 (C-4), 171.1 (C = O),
173.6 (C = O) ppm.
[
13CN]-5-cyano-3-(methoxycarbonylethyl)-4-(methoxycarbo-
nylmethyl)-pyrrole (7c)
Similarly, [13CN]-5-cyano-3-(methoxycarbonylethyl)-4-(tetrahydrop-
yran-20-yloxyethyl)-pyrrole 6c (2.45 g, 8 mmol) yielded [13CN]-5-
cyano-4-(methoxycarbonylethyl)-3-(hydroxyethyl)-pyrrole (1.40g,
[4-13C]-5-cyano-3-(methoxycarbonylethyl)-4-(methoxycar-
bonylmethyl)-pyrrole (7a)
79%). 1H-NMR (300 MHz, acetone-d6): d = 2.58 (t, JH;H = 7.3Hz,
3
Similarly, [4-13C]-5-cyano-3-(methoxycarbonylethyl)-4-(tetrahydropyr-
an-20-yloxyethyl)-pyrrole 6a (2.45 g, 8 mmol) yielded 5-cyano-4-
(methoxycarbonylethyl)-3-(hydroxyethyl)-pyrrole (1.51 g, 85%).
3
3
2H), 2.76 (t, JH;H = 7.3 Hz, 2H), 2.80 (t, JH;H = 7.2 Hz, 2H), 3.62 (s,
3
3
OCH3), 3.70 (dt, JH;H = 7.2Hz, JH;H = 5.6 Hz, 2H), 3.88 (bt,
4
3JH;H = 5.6Hz, 1H), 6.90 (dd, JH;H = 2.9Hz, JH,C = 2.1Hz, 1H),
3
1H-NMR (300 MHz, acetone-d6): d=2.58 (t, JH;H = 7.3 Hz, 2H), 2.76
3
10.87 (bs, NH) ppm. 13C-NMR (75 MHz, acetone-d6): d = 20.8, 29.3,
2
(t, JH;H =7.3Hz, 2H), 2.80 (dt, JH,C =6.1Hz, JH;H = 7.2 Hz, 2H), 3.62
3
3
35.2, 51.6 (OCH3), 62.8, 100.5 (d, JC,C = 99 Hz, C-5), 114.9 (13C-
1
3
(s, OCH3), 3.70 (ddt, 3JH;H =7.2Hz, 3JH;H =5.6Hz, JH,C
=
3
labeled, intense peak, CN), 122.5 (d, JC,C = 3.2Hz, C-2), 123.5 (d,
3
3
3JC,C = 5.0Hz, C-3), 131.2 (d, JC,C = 5.3Hz, C-4), 173.6 (C =O)ppm.
2
4.1 Hz, 2H), 3.81 (bt, JH;H = 5.6 Hz, 1H), 6.90 (dd, JH,C =6.9Hz,
3JH;H = 2.9 Hz, 1H), 10.85 (bs, NH) ppm. 13C-NMR (75 MHz, acetone-
HRMS calculated for 13C1C10H14N2O3, [M]1: 223.1038; found:
223.1022.
1
d6): d= 20.8, 29.3 (d, JC,C =48Hz, CH2), 35.2, 51.6 (OCH3), 62.8 (d,
2JC,C =2.0Hz, CH2), 100.5 (d, 1JC,C = 72 Hz, C-5), 114.9 (d, 2JC,C =5.3Hz,
Similarly, [13CN]-5-cyano-4-(methoxycarbonylethyl)-3-(hydro-
xyethyl)-pyrrole (1.40 g, 6.3 mmol) afforded 7c (0.65 g, 41%).
1H-NMR (300 MHz, CDCl3): d = 2.58 (bt, 3JH;H = 7.3 Hz, 2H), 2.74 (t,
3JH;H = 7.3 Hz, 2H), 3.63 (s, 2H), 3.67 (s, OCH3), 3.73 (s, OCH3) 6.72
(dd, 3JH;H = 2.8 Hz, 4JH,C = 2.0 Hz, 1H), 8.87 (bs, NH) ppm. 13C-NMR
2
1
CN), 122.5 (d, JC,C = 2.5 Hz, C-2), 123.5 (d, JC,C = 54 Hz, C-3), 131.2
(13C-labeled, intense peak, C-4), 173.6 (C = O) ppm. HRMS calculated
for 13C1C10H14N2O3, [M]1: 223.1038; found: 223.1025.
Similarly, 5-cyano-4-(methoxycarbonylethyl)-3-(hydroxyethyl)-pyr-
1
role (1.35 g, 6 mmol) afforded 7a (0.51 g, 34%). H-NMR (300 MHz,
3
(75 MHz, CDCl3): d = 20.0, 30.2 (d, JC,C = 0.7 Hz, CH2), 34.3, 51.7
3
3
1
(OCH3), 52.2 (OCH3), 100.7 (d, JC,C = 101 Hz, C-5), 113.8 (13C-
CDCl3): d=2.58 (bt, JH;H = 7.3 Hz, 2H), 2.74 (dt, JH;H =7.3Hz ,
3JH,C = 4.0 Hz, 2H), 3.63 (d, JH,C = 6.5 Hz, 2H), 3.67 (s, OCH3), 3.73
2
3
labeled, intense peak, CN), 121.8 (d, JC,C = 3.6 Hz, C-2), 123.3 (d,
3
(s, OCH3), 6.72 (dd, JH,C =3.0Hz, JH;H = 6.8 Hz, 1H), 8.96 (bs,
3
2
3JC,C = 5.0 Hz, C-3), 125.6 (d, JC,C = 5.1 Hz, C-4), 171.1 (d,
NH) ppm. 13C-NMR (75 MHz, CDCl3): d= 20.8 (d, JC,C =2.8Hz, CH2),
30.2 (d, JC,C =50Hz, CH2), 34.3 (d, JC,C =1.8Hz, CH2), 51.7 (OCH3),
2
4JC,C = 0.8 Hz, C = O), 173.5 (C = O) ppm. HRMS calculated for
1
3
13C1C11H14N2O4, [M]1: 251.0987; found: 251.0964.
52.2 (OCH3), 100.7 (d, 1JC,C = 74 Hz, C-5), 113.8 (d, 2JC,C =5.1Hz, CN),
121.8 (d, JC,C = 2.8 Hz, C-2), 122.8 (d, JC,C = 56 Hz, C-3), 125.6 (13C-
2
1
Porphobilinogen lactam methyl ester (8)
2
labeled, intense peak, C-4), 171.1 (d, JC,C = 2.9 Hz), 173.5
(C=O)ppm. HRMS calculated for 13C1C11H14N2O4, [M]1: 251.0987;
found: 251.0964.
To a solution of 7 (0.51 g, 2 mmol) in EtOH (50 mL) Pd-black
(0.15 g, 1.4 mmol) and PtO2 (0.37 g, 1.6 mmol) were added to the
J. Label Compd. Radiopharm 2009, 52 341–349
Copyright r 2009 John Wiley & Sons, Ltd.