Glucopyranoside Recognition
J . Org. Chem., Vol. 64, No. 22, 1999 8175
g, 40.8 mmol) was added BrCCl3 (7.88 mL) at room temper-
ature. The reaction mixture was refluxed for 1.5 h and filtered.
The filtrate was evaporated and chromatographed (silica gel;
eluent, CH2Cl2) to give 14: yield 52% (6.99 g); mp 151-153
extract was evaporated and chromatographed (silica gel;
eluent, CH2Cl2) to give 18: yield 73% (605 mg); mp 149-150
°C; IR (KBr) 3332, 3236, 2106, 1660 cm-1; 1H NMR (CDCl3) δ
3.18 (s, 1 H), 3.52 (s, 3 H), 5.25 (s, 2 H), 7.13 (d, J ) 8.8 Hz, 2
H), 7.27 (d, J ) 7.9 Hz, 1 H), 7.74 (t, J ) 7.9 Hz, 1 H), 7.87 (d,
1
°C; IR (KBr) 3317, 1668 cm-1; H NMR (CDCl3) δ 3.50 (s, 3
H), 5.25 (s, 2 H), 7.13 (d, J ) 8.7 Hz, 2 H), 7.25 (d, J ) 7.6 Hz,
1 H), 7.61 (t, J ) 7.6 Hz, 1 H), 7.87 (d, J ) 8.7 Hz, 2 H), 8.35
(d, J ) 7.6 Hz, 1 H), 8.46 (br s, 1 H); 13C NMR (CDCl3) δ 56.28,
94.11, 112.39, 116.12, 123.48, 126.77, 129.09, 139.22, 140.66,
151.69, 160.65, 164.89; FABMS (in 3-nitrobenzyl alcohol) m/e
(rel intensity) 337 (MH+, 100%), 339 (MH+ + 2, 100%). Anal.
Calcd for C14H13O3N2Br: C, 49.87; H, 3.89; N, 8.31. Found:
C, 49.33; H, 3.78; N, 7.86.
N-2-[6-(3-Hyd r oxy-3-m eth yl-1-bu tyn yl)p yr id yl]-3-n -oc-
toxyben za m id e (15). To an Et2NH (22 mL) solution of 13
(2.28 g, 5.6 mmol), (Ph3P)2PdCl2 (79 mg, 0.11 mmol), and CuI
(11 mg, 0.056 mmol) was added 2-methyl-3-butyn-2-ol (522 mg,
6.2 mmol) dropwise at 0 °C. The reaction mixture was stirred
at room temperature for 5.5 h. After removal of the solvent,
the residue was chromatographed (silica gel; eluent, CH2Cl2)
to give 15: yield 97% (1.27 g); mp 101-102 °C; IR (KBr) 3336,
1681 cm-1; 1H NMR (CDCl3) δ 0.89 (t, J ) 6.9 Hz, 3 H), 1.30-
1.49 (m, 10 H), 1.66 (s, 6 H), 1.81 (quint, J ) 6.9 Hz, 2 H),
2.53 (br s, 1 H), 4.02 (t, J ) 6.9 Hz, 2 H), 7.10 (d, J ) 8.1 Hz,
1 H), 7.21 (d, J ) 8.1 Hz, 1 H), 7.38 (t, J ) 8.1 Hz, 1 H), 7.44-
7.46 (m, 2 H), 7.72 (t, J ) 8.1 Hz, 1 H), 8.38 (d, J ) 8.1 Hz, 1
H), 8.70 (br s, 1 H); 13C NMR (CDCl3) δ 14.08, 22.62, 25.96,
29.13, 29.20, 29.30, 31.22, 31.77, 65.27, 68.21, 80.62, 94.16,
113.02, 113.81, 119.02, 119.11, 123.24, 129.67, 135.15, 138.75,
140.60, 151.55, 159.50, 165.64; FABMS (in 3-nitrobenzyl
alcohol) m/e (rel intensity) 409 (MH+, 100%). Anal. Calcd for
J ) 8.8 Hz, 2 H), 8.41 (d, J ) 7.9 Hz, 1 H), 8.52 (br s, 1 H); 13
C
NMR (CDCl3) δ 56.25, 77.15, 82.15, 94.10, 114.29, 116.08,
123.40, 127.00, 129.04, 138.72, 140.04, 151.64, 160.52, 165.03;
FABMS (in 3-nitrobenzyl alcohol) m/e (rel intensity) 283 (MH+,
100%). Anal. Calcd for C16H14O3N2: C, 68.08; H, 5.00; N, 9.92.
Found: C, 67.45; H, 4.79; N, 9.65.
Acyclic Recep tor 2. To an Et2NH (20 mL) solution of 2,6-
dibromopyridine (614 mg, 2.6 mmol), (Ph3P)2PdCl2 (73 mg,
0.104 mmol), and CuI (10 mg, 0.052 mmol) was added an Et2-
NH (30 mL) solution of 17 (2.0 g, 5.7 mmol) dropwise at 0 °C.
The reaction mixture was stirred at room temperature for 12
h. After removal of the solvent, the residue was dissolved in
water and extracted with CH2Cl2. The CH2Cl2 extract was
evaporated, chromatographed (silica gel; eluent, CH2Cl2), and
washed with AcOEt to give 2: yield 65% (1.32 g); mp 169-
171 °C; IR (KBr) 3437, 1676 cm-1; 1H NMR (CDCl3) δ 0.89 (t,
J ) 6.8 Hz, 6 H), 1.30-1.50 (m, 20 H), 1.82 (quint, J ) 6.8
Hz, 4 H), 4.03 (t, J ) 6.8 Hz, 4 H), 7.11 (d, J ) 7.5 Hz, 2 H),
7.37-7.46 (m, 8 H), 7.62 (d, J ) 7.5 Hz, 2 H), 7.73-7.82 (m, 3
H), 8.45 (d, J ) 7.5 Hz, 2 H), 8.61 (br s, 2 H); 13C NMR (CDCl3)
δ 14.09, 22.64, 25.97, 29.14, 29.21, 29.30, 31.78, 68.28, 87.27,
87.62, 112.80, 114.51, 118.80, 119.33, 124.15, 127.33, 129.83,
135.24, 136.67, 138.83, 140.26, 142.97, 151.64, 159.58, 165.63;
FABMS (in 3-nitrobenzyl alcohol) m/e (rel intensity) 776 (MH+,
100%). Anal. Calcd for C31H53O2N2: C, 75.84; H, 6.88; N, 9.03.
Found: C, 75.70; H, 6.94; N, 8.88.
C
25H32O3N2: C, 73.50; H, 7.89; N, 6.86. Found: C, 73.02; H,
N,N′-[4-(Meth oxym eth oxy)ben zoyl]-2,6-bis[(6-am in opy-
r id -2-yl)eth yn yl]p yr id in e (9a ). An Et3N (11 mL) solution
of 2,6-dibromopyridine (221 mg, 0.913 mmol), 18 (569 mg, 2.01
mmol), (Ph3P)2PdCl2 (26 mg, 0.0365 mmol), and CuI (4 mg,
0.01825 mmol) was stirred at 60 °C for 4 h. After removal of
the solvent, the residue was chromatographed (silica gel;
eluent, CH2Cl2) and washed with AcOEt to give 9a : yield 78%
(454 mg); mp 194-196 °C; IR (KBr) 3435, 1670 cm-1; 1H NMR
(CDCl3) δ 3.50 (s, 6 H), 5.25 (s, 4 H), 7.14 (d, J ) 8.8 Hz, 4 H),
7.42 (d, J ) 7.6 Hz, 2 H), 7.61 (d, J ) 7.6 Hz, 2 H), 7.73-7.81
(m, 3 H), 7.89 (d, J ) 8.8 Hz, 4 H), 8.44 (d, J ) 7.6 Hz, 2 H),
8.56 (br s, 2 H); 13C NMR (CDCl3) δ 56.25, 87.20, 87.66, 94.10,
114.48, 116.08, 123.98, 127.04, 127.28, 129.08, 136.65, 138.77,
140.17, 142.95, 151.78, 160.54, 165.08; FABMS (in 3-nitroben-
zyl alcohol) m/e (rel intensity) 640 (MH+, 100%). Anal. Calcd
for C37H29O3N5: C, 69.47; H, 4.57; N, 10.94. Found: C, 69.35;
H, 4.38; N, 10.64.
7.89; N, 6.56.
N-2-[6-(3-Hydr oxy-3-m eth yl-1-bu tyn yl)pyr idyl]-4-(m eth -
oxym eth oxy)ben za m id e (16). To an Et2NH (100 mL) solu-
tion of 14 (6.74 g, 20 mmol), (Ph3P)2PdCl2 (281 mg, 0.4 mmol),
and CuI (39 mg, 0.2 mmol) was added 2-methyl-3-butyn-2-ol
(1.58 g, 22 mmol) dropwise at 0 °C. The reaction mixture was
stirred at room temperature for 4 h. After removal of the
solvent, the residue was chromatographed (silica gel; eluent,
CH2Cl2/AcOEt 10:1) to give 16: yield 96% (6.5 g); mp 116-
117 °C; IR (KBr) 3365, 1682 cm-1; 1H NMR (CDCl3) δ 1.67 (s,
6 H), 3.00 (br s, 1 H), 3.50 (s, 3 H), 5.25 (s, 2 H), 7.12 (d, J )
8.5 Hz, 2 H), 7.19 (d, J ) 7.9 Hz, 1 H), 7.71 (t, J ) 7.9 Hz, 1
H), 7.92 (d, J ) 8.5 Hz, 2 H), 8.38 (d, J ) 7.9 Hz, 1 H), 8.76 (br
s, 1 H); 13C NMR (CDCl3) δ 31.22, 56.22, 65.24, 80.62, 94.05,
94.08, 113.78, 115.93, 123.06, 127.00, 129.26, 138.70, 140.46,
151.70, 160.46, 165.15; FABMS (in 3-nitrobenzyl alcohol) m/e
(rel intensity) 341 (MH+, 100%). Anal. Calcd for C19H20O4N2:
C, 67.05; H, 5.92; N, 8.23. Found: C, 67.13; H, 5.88; N, 7.94.
N-2-(6-Eth yn ylp yr id yl)-3-n -octoxyben za m id e (17). A
toluene (30 mL) solution of 15 (2.68 g, 6.58 mmol) and NaH
(27 mg, 0.658 mmol; commercial 60% dispersion was washed
thoroughly with hexane prior to use) was stirred at 120 °C for
40 min and evaporated. The residue was dissolved in water
and extracted with CH2Cl2. The CH2Cl2 extract was evaporated
and chromatographed (silica gel; eluent, CH2Cl2/hexane 1:1)
to give 17: yield 88% (2.05 g); mp 54-56 °C; IR (KBr) 3435,
N,N′-[4-(Meth oxym eth oxy)ben zoyl]-2,6-bis[(6-am in opy-
r id -2-yl)eth yn yl]-4-n -bu toxyp yr id in e (9b). This compound
was synthesized from 4-n-butoxy-2,6-dibromopyridine5 (463
mg, 1.5 mmol) and 18 (960 mg, 3.35 mmol) in a manner similar
to that described for 9a . 9b: yield 50% (530 mg); mp 163-
165 °C; IR (KBr) 3361, 1676 cm-1; 1H NMR (CDCl3) δ 1.00 (t,
J ) 7.3 Hz, 3 H), 1.50 (sext, J ) 7.3 Hz, 2 H), 1.81 (quint, J )
7.3 Hz, 2 H), 3.51 (s, 6 H), 4.05 (t, J ) 7.3 Hz, 2 H), 5.25 (s, 4
H), 7.12-7.16 (m, 6 H), 7.42 (d, J ) 7.9 Hz, 2 H), 7.78 (t, J )
7.9 Hz, 2 H), 7.89 (d, J ) 8.8 Hz, 4 H), 8.43 (d, J ) 7.9 Hz, 2
H), 8.56 (br s, 2 H); 13C NMR (CDCl3) δ 13.72, 19.05, 30.70,
56.27, 68.39, 87.02, 87.46, 94.13, 114.35, 114.43, 116.10,
124.01, 127.07, 129.09, 138.77, 140.25, 143.87, 151.77, 160.55,
165.10, 165.33; FABMS (in 3-nitrobenzyl alcohol) m/e (rel
intensity) 712 (MH+, 100%). Anal. Calcd for C41H37O7N5: C,
69.19; H, 5.24; N, 9.84. Found: C, 68.44; H, 5.05; N, 9.19.
N,N′-(4-Hyd r oxyben zoyl)-2,6-bis[(6-a m in op yr id -2-yl)-
eth yn yl]p yr id in e (10a ). An i-PrOH-THF (15 + 15 mL)
solution of 9a (461 mg, 0.65 mmol) and (+)-(S)-camphor-10-
sulfonic acid monohydrate (1.14 g, 4.55 mmol) was stirred at
80 °C for 4 h. Solid NaHCO3 was added to the reaction mixture
until no more CO2 evolved. After removal of the solvent, the
residue was continuously extracted with THF by a Soxhlet
extractor for 1.5 days. The THF extract was evaporated, and
the residue was washed with CH2Cl2 and MeOH to give 10a :
3265, 3219, 2108, 1680 cm-1; H NMR (CDCl3) δ 0.89 (t, J )
1
6.9 Hz, 3 H), 1.29-1.51 (m, 10 H), 1.81 (quint, J ) 6.9 Hz, 2
H), 3.18 (s, 1 H), 4.02 (t, J ) 6.9 Hz, 2 H), 7.10 (d, J ) 8.0 Hz,
1 H), 7.29 (d, J ) 8.0 Hz, 1 H), 7.36-7.44 (m, 3 H), 7.75 (t, J
) 8.0 Hz, 1 H), 8.42 (d, J ) 8.0 Hz, 1 H), 8.58 (br s, 1 H); 13C
NMR (CDCl3) δ 14.06, 22.60, 25.93, 29.10, 29.18, 29.27, 31.75,
68.23, 77.20, 82.08, 112.71, 114.29, 118.78, 119.27, 123.53,
129.79, 135.17, 138.74, 140.07, 151.47, 159.52, 165.54; FABMS
(in 3-nitrobenzyl alcohol) m/e (rel intensity) 351 (MH+, 100%).
Anal. Calcd for C22H26O2N2: C, 75.40; H, 7.47; N, 7.99.
Found: C, 75.56; H, 7.75; N, 7.63.
N -2-(6-E t h yn ylp yr id yl)-4-(m e t h oxym e t h oxy)b e n za -
m id e (18). A toluene (12 mL) solution of 16 (998 mg, 2.93
mmol) and NaH (12 mg, 0.293 mmol; commercial 60% disper-
sion was washed thoroughly with hexane prior to use) was
stirred at 120 °C for 40 min and evaporated. The residue was
dissolved in water and extracted with CH2Cl2. The CH2Cl2
yield 75% (269 mg); mp 268-271 °C; IR (KBr) 3385, 1678 cm-1
1H NMR (DMSO-d6) δ 6.84 (d, J ) 8.1 Hz, 4 H), 7.50 (d, J )
;