KA Evans, CT Kane, CM Tice
ꢀ463mg). The solid was puri®ed by trituration with
saturated sodium hydrogen carbonate ꢀ2Â20ml),
water ꢀ3Â20ml) and acetonitrile ꢀ3Â20ml). The
resulting solid was dried under vacuum at room
temperature to give 3 ꢀ175mg, 31%) asa white solid;
mp 138±142°C ꢀwith prior softening); 1H NMR
ꢀhexadeuterodimethyl sulfoxide, 500MHz): d 10.3
ꢀs, 1H), 7.92 ꢀt, 1H, J =5.5Hz), 7.70 ꢀt, 1H, J =
5.3Hz), 6.37 ꢀs, 1H), 6.32 ꢀs, 1H), 4.30 ꢀm, 1H), 4.26
ꢀs, 3H), 4.13 ꢀm, 1H), 3.16 ꢀdd, 2H, J =6.6, 12.8Hz),
3.10 ꢀm, 1H), 3.03 ꢀdd, 2H, J =6.5, 12.7Hz), 2.82
ꢀdd, 1H, J =5.1, 12.4Hz), 2.58 ꢀd, 1H, J = 12.4Hz),
2.04 ꢀt, 2H, J =7.4Hz), 1.63±1.25 ꢀm, 12H); 13C
NMR ꢀhexadeuterodimethyl sulfoxide, 75MHz): d
171.8, 162.7, 158.5, 151.5, 126.8, 108.7, 66.1, 61.1,
69.2, 55.5, 38.3, 35.2, 28.9, 28.8, 28.2, 28.1, 25.4,
23.7; two 13C resonances of 3 are obscured by DMSO-
d6 signals; MS ꢀESI) m/z 480 ꢀM-H); IR ꢀpotassium
bromide): 3295, 2935, 2862, 1703, 1641, 1545, 1494,
847mg, 7.49mmol) in tetrahydrofuran ꢀ33ml) was
added dropwise to sodium hydride ꢀ297mg,
7.43mmol, 60% dispersion in mineral oil) at 20°C
under an argon atmosphere. The suspension was
cooled to 0±5°C, and a solution of 12 ꢀ2.20g,
6.26mmol) in tetrahydrofuran ꢀ22ml) wasadded
dropwise. When the addition was complete, the
reaction mixture washeated at re¯ux for 9h and then
stirred at 20°C for 16h. The reaction mixture was
diluted with ethyl acetate ꢀ200ml), washed with water
ꢀ4Â50ml), dried ꢀmagnesium sulfate), and concen-
trated to give the crude product ꢀ3.1g). The crude
material waspuri®ed by column chromatography
ꢀ230g of silica gel eluted with ethyl acetate followed
by ethyl acetate methanol, 982 by volume, until
product began to elute, then ethyl acetate methanol,
955 by volume) to give 13 ꢀ1.9g, 79%), asa light
1
yellow oil, H NMR ꢀhexadeuterodimethyl sulfoxide,
400MHz): d 8.02 ꢀs, 1H), 7.94 ꢀs, 1H), 7.83 ꢀt, 1H,
J =5.1Hz), 6.77 ꢀt, 1H, J =4.2Hz), 4.42 ꢀt, 2H,
J =6.6Hz), 3.03 ꢀdd, 2H, J =6.6, 12.8Hz), 2.90 ꢀdd,
2H, J =6.6, 13.2Hz), 2.18 ꢀt, 2H, J =7.0Hz), 1.97 ꢀt,
2H, J =7.0Hz), 1.39 ꢀs, 9H), 1.39±1.34 ꢀm, 4H),
1.27±1.22 ꢀm, 2H).
1460, 1264, 1241, 1149, 1069, 867, 762, 609cmÀ1
.
No syn/anti determinations were performed for
compoundswith an alkoxyimine moiety; however,
1H and 13C NMR spectra of the 3 and 4 indicate that
they are single isomers and, by analogy with com-
poundsprepared by ims ilar methodsꢀReferences
11±13), they are assumed to possess the E con®gura-
tion.
2.2.7 N-[5-[[4-ꢀ2-Amino-1-cyano-2-oxoethylidene)-
amino]oxy]-1-oxobutyl]-1,5-diaminopentane p-toluene-
sulfonate salt ꢀ14)
2.2.5 N-tert-Butoxycarbonyl-N'-[5-ꢀ4-bromo-1-
oxobutyl)]-1,5-diaminopentane ꢀ12)
A solution of 13 ꢀ907mg, 2.37mmol), in 50%
tri¯uoroacetic acid in dichloromethane ꢀ8.8ml) was
stirred at 0±5°C for 0.5h. p-Toluenesulfonic acid
monohydrate ꢀ450mg, 2.37mmol) wasadded, the
reaction mixture wasstirred at room temperature for
15min. and then concentrated to dryness. The residue
wasco-evaporated with dichloromethane ꢀ3 Â10ml)
then the residue was triturated with tert-butyl methyl
ether ꢀ75ml) at room temperature for 0.5h. The
solvent was decanted from the oily solid residue, which
was dissolved in ethanol ꢀ5ml) and diluted with diethyl
ether ꢀ75ml). The resulting suspension was stirred at
room temperature for 0.5h and then stored at À10°C
for 0.5h. The solvent was decanted and the solid was
dried under vacuum at room temperature to give 14
ꢀ1.05g, 97%), asa white oslidi®ed foam, 1H NMR
ꢀhexadeuterodimethyl sulfoxide, 400MHz): d 8.02 ꢀs,
1H), 7.96 ꢀs, 1H), 7.85 ꢀt, 1H, J =5.9Hz), 7.62 ꢀbs,
3H), 7.49 ꢀd, 2H, J =8.1Hz), 7.13 ꢀd, 2H,
J =8.1Hz), 4.44 ꢀt, 2H, J =6.2Hz), 3.07±3.03 ꢀdd,
2H J =6.6, 12.5Hz), 2.79±2.77 ꢀm, 2H), 2.31 ꢀs, 3H),
2.20 ꢀt, 2H, J =7.0Hz), 2.01±1.95 ꢀm, 2H), 1.58±
1.50 ꢀm, 2H), 1.46±1.39 ꢀm, 2H), 1.34±1.30 ꢀm, 2H).
To
a solution of 4-bromobutyric acid ꢀ2.49g,
14.9mmol) in tetrahydrofuran ꢀ55ml) at À3°C
ꢀice±sodium chloride bath) under an argon atmos-
phere wasadded dropwise 1-methylpiperidine ꢀ1.48g,
14.9mmol) followed by isobutyl chloroformate
ꢀ1.93g, 14.9mmol). The reaction mixture wasstirred
at À3°C for 15min., then 1-methylpiperidine ꢀ1.48g,
14.9mmol) wasadded dropwies, followed by the
dropwise addition of a solution of N-tert-butoxycarbo-
nyl-1,5-diaminopentane ꢀ2.50g, 12.4mmol) in tetra-
hydrofuran ꢀ20ml). The reaction mixture wasstirred
at 0° to À3°C for 3h, then ®ltered and the ®lter cake
washed with tetrahydrofuran ꢀ3Â25ml). The com-
bined ®ltrate and washings were concentrated to
dryness to give a light yellow oil. The oil was puri®ed
by column chromatography ꢀ280g of silica gel eluted
with ethyl acetate hexanes, 31 by volume) to give
12 ꢀ2.55g, 49%) as a viscous, colorless oil that
solidi®ed on standing at À20°C to give a white solid,
1H NMR ꢀdeuterochloroform, 500MHz): d 5.63 ꢀbm,
1H), 4.55 ꢀbm, 1H), 3.48 ꢀt, 2H, J =6.3Hz), 3.25
ꢀdd, 2H, J =6.8, 12.9Hz), 3.11 ꢀbd, 2H, J =6.0Hz),
2.35 ꢀt, 2H, J =7.0Hz), 2.22±2.17 ꢀm, 2H), 1.62±
1.47 ꢀm, 4H), 1.44 ꢀs, 9H), 1.38±1.32 ꢀm, 2H); MS
2.2.8 ꢀ3aS,4S,6aR)-N-[5-[[4-[[ꢀ2-amino-1-cyano-2-
oxoethylidene)amino]oxy]-1-oxobutyl]amino]pentyl]-
hexahydro-2-oxo-1H-thieno[3,4-d]imidazole-4-
pentanamide ꢀ4)
ꢀESI) m/z 351 ꢀMH) , 373 ꢀMNa) .
2.2.6 N-tert-Butoxycarbonyl-N'-[5-[[4-ꢀ2- amino-1-
cyano-2-oxoethylidene)amino]oxy]-1-oxobutyl]-1,5-
diaminopentane ꢀ13)
To a suspension of 14 ꢀ613mg, 1.35mmol) and N-
hydroxysuccinimidobiotin ꢀ460mg, 1.35mmol) in
N,N-dimethylformamide ꢀ6.4ml) at 5°C wasadded
triethylamine ꢀ460ml, 3.30mmol). The reaction ¯ask
A solution of 2-cyano-2-ꢀhydroxyimino)acetamide ꢀ5,
394
Pest Manag Sci 58:392±396 ꢀonline: 2002)