N-( (R )-l-Methylpropyl)-9,lO-didehydro-6-methylergoline-
B&carboxamide (2). (+)-Lysergic acid monohydrate
(150 mg, 0.52 mmol) and 25 mL of dry, ethanol-free CHCl, were
placed in a flamedried 50 d, three-necked, round-bottom flask
equipped with a condenser, N2 line, and septa inlets. The stirred
slurry was brought to reflux in a preheated 90 "C oil bath after
which 384 mg (5.2 mmol) of (R)-(-)-2-butylamine (Aldrich) in 1.0
simultaneously, via syringe, over 3 min. The mixture was allowed
to stir at reflux for an additional 5 min and was then cooled to
room temperature. The clear amber CHC13 solution was then
washed with 1 M NHdOH (3 x 30 mL) and brine (1 X 10 mL)
and dried (Na,SO,). The drying agent was removed by fitration,
and the solution was concentrated in the dark by rotary evaporation
at 30 "C.
The residue was purXed and fractionated by radial centrifugal
chromatography (Chromatotron, Harrison Research) using a silica
gel rotor and eluting with ethyl acetate in an N2-ammonia atmosphere.
TLC (silica gel, EtOAeNH3) showed a large blue
fluorescent product spot at R, 0.21 corresponding to the (R)-2-
butyllprgamide and a much smaller spot at Rf 0.15 corresponding
to the S isomer. The faster moving component was collected and
concentrated by rotary evaporation. The residue was taken up
into CH2ClZ, washed with HzO, and dried (MgSOJ, and the
CHzClz was removed by rotary evaporation followed by pumping
under high vacuum. The free base (158 mg, 94% yield) was taken
up into 2 mL of methanol, and 57 mg of maleic acid in 0.75 mL
of methanol was added. The maleate salt (1:l stoichiometry)
spontaneously crystallized as a white crystalline solid mp 210
"C dec; lH NMR (free base, CDClJ S 0.91 (t, J = 7.5 Hz, 3 H),
1.13 (d, J = 6.7 Hz, 3 H), 1.36-1.56 (m, 2 H), 2.60 (s,3 H), 2.68-2.82
(m, 2 H), 3.05-3.13 (m, 1 H), 3.31-3.56 (m, 3 H), 3.89-3.98 (m,
(m, 3 H), 8.15 (br 8, 1 H); [(Y]D = +48" (c = 0.1, HZO); IR (free
base, neat) 1650 cm-l (C=O). Anal. (CzrH&I3O5) C, H, N.
N - (( S ) - 1 -Met hylpropyl)-g, 1 0-didehydro-6-met hylergolina88-
carboxamide (3). An exact replication of the above
procedure using 150 mg of (+)-lysergic acid monohydrate and 384
mg of (S)-(+)-2-butylamine (Aldrich) gave 154 mg (91.7% yield)
of the free base. The free base in methanol was combined with
55 mg of maleic acid in methanol to again yield a white aytalline
solid with 1:l stoichiometry: mp 213 "C dec; 'H NMR (free base,
CDC13) 6 0.93 (t, J = 7.5 Hz, 3 H), 1.13 (d, J = 6.7 Hz, 3 H),
1.37-1.58 (m, 2 H), 2.60 (a, 3 H), 2.66-2.82 (m, 2 H), 3.05-3.13
(m, 1 H), 3.31-3.56 (m, 3 H), 3.89-3.98 (m, 1 H), 6.45 (e, 1 H),
6.60 (d, J = 8.0 Hz, 1 H), 6.92 (8, 1 H), 7.12-7.23 (m, 3 H), 8.02
(br 8, 1 H); [(Y]D = +59" (c = 0.1, HzO); IR (free base, neat) 1650
cm-l ( C 4 ) . Anal. (CurH~N305) C, H, N.