1
150
B. A. CZESKIS ET AL.
4
8) (330 mg, 1.16 mmol) in one portion. The reaction mixture was
(
heated at 80–838C for 16 h and evaporated under vacuum. The
residue was subjected to flash chromatography, eluting with one
column volume of chloroform/methanol (90:10) following by
three
column
volumes
of
chloroform/methanol/ammonium
1
hydroxide (90:10:1) to give LY368842-[indole- C] (378 mg, 82%)
4
as a pale solid. TLC: R = 0.31 (chloroform/methanol/ammonium
f
hydroxide 90:10:1). The compound co-eluted with an authentic
sample of LY368842 by HPLC and TLC under the above conditions.
For non-radioactive compound (prepared in model experiment):
1
H-NMR (CD OD, d, ppm): 1.10 (d, J = 3.4 Hz, 6 H), 2.75 (d, J =
3
5
.4 Hz, 2 H), 2.85 (m, 1 H), 2.99 (m, 1 H), 4.09 (m, 3 H), 6.45 (dd, J =
4
.9 and 3.4 Hz, 1 H), 6.49 (d, J = 3.4 Hz, 1 H), 6.88–6.94 (m, 5 H), 7.05
(d, J = 2.9 Hz, 1 H), 7.23 (d, J = 8.8 Hz, 2 H), 8.18 (dd, J = 8.8 and
2
.4 Hz, 1 H), 8.57 (d, J = 2.4 Hz).
14
(
methylpropyl]phenoxy]pyridine-5-carboxamide glycolate,
S)-2-[4-[2-[3-(Indol-2-[ C]-4-yloxy)-2-hydroxypropylamino]-2-
1
4
(
LY368842-[indole- C]) glycolate
1
4
To a solution of free base LY368842-[indole- C] (215 mg, 0.45 mmol) in
ethanol (1.4 ml) was added a solution of glycolic acid (35 mg,
0
3
.46 mmol) in ethanol (1.0 ml). The reaction mixture was stirred for
0 min at room temperature and evaporated under vacuum. The residue
was triturated with ethyl ether (3 Â 10 ml), and the supernatant liquid
was decanted each time. After drying under vacuum, LY368842-
1
4
indole- C] glycolate (246 mg, 99%) was obtained as a white solid. The
[
radiochemical purity was determined to be 98.4% by radio-HPLC:
Zorbax SB-Phenyl column (4.6 Â 250 mm); flow rate: 1.0 ml/min;
column temperature: 408C; detection: UV 260 nm; mobile phase:
methanol/0.1% trifluoroacetic acid. The specific activity of the product
was 60.4 mCi/mg. The compound co-eluted with an authentic sample of
LY368842 glycolate by HPLC under the above conditions. For non-
1
radioactive compound (prepared in model experiment): H-NMR
(
(
DMSO-d , d, ppm): 1.01 (d, J = 3.4 Hz, 6 H), 2.70 (s, 2 H), 2.82
m, 1 H), 2.95 (m, 1 H), 3.72 (s, 2 H), 4.01 (m, 3 H), 6.38–6.43 (m, 2 H),
6
6.88–6.99 (m, 5 H), 7.14 (m, 1 H), 7.18 (d, J = 8.8 Hz, 2 H), 7.42 (s, 1 H),
7.97 (s, 1 H), 8.18 (dd, J = 8.3 and 2.4 Hz, 1 H), 8.56 (d, J = 2.4 Hz,
1 H), 11.00 (s, 1 H).
Copyright # 2002 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2002; 45: 1143–1152