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Can. J. Chem. Vol. 88, 2010
2
3
freshly distilled THF were used. 8f was obtained in a 65%
yield (81 mg). H NMR (CDCl3, 400 MHz) d: 6.77–6.73
2H), 4.46 (dt, JHF = 47.2 Hz, JHH = 6.0 Hz, 2H), 3.48–
1
3.45 (m, 2H), 2.61–2.56 (m, 2H), 2.48–2.43 (m, 2H), 2.47
(s, 3H), 1.90–1.83 (m, 2H), 1.79–1.68 (m, 2H), 1.53–148
(m, 1H), 3.85–3.80 (m, 2H), 3.75–3.71 (m, 2H), 3.69–3.66
(m, 4H), 3.63–3.59 (m, 2H), 3.53–3.49 (m, 2H), 3.45–3.42
(m, 2H), 2.63–2.58 (m, 2H), 2.51–2.45 (m, 2H), 2.42 (s,
3H). HR-MS: calcd. for C14H24N3O4S [M + 1]: 330.1482;
found: 330.1476. EA calcd.: C 51.04, H 7.04, N 12.76;
found: C 50.07, H 6.89, N 12.52.
2
(m, 4H). 19F NMR (CDCl3, 376 MHz) d: –218.79 (tt, JHF
=
3
47.2 Hz, JHF = 25.3 Hz). HR-MS calcd. for C14H23FN3OS
[M + 1]: 300.1540; found: 300.1536. EA calcd.: C 56.16, H
7.41, N 14.03; found: C 56.58, H 7.39, N 13.77.
3-(7-Fluoroheptyloxy)-4-(1-methyl-1,2,5,6-
tetrahydropyridin-3-yl)-1,2,5-thiadiazole (9d)
3-(3-Fluoropropoxy)-4-(1-methyl-1,2,5,6-tetrahydropyridin-
3-yl)-1,2,5-thiadiazole (9a)
Compound 9d was prepared in an analogous manner to
that of 9a, where 0.4 mmol of 7d was used followed by
1.4 mmol of 60% NaH and 0.23 mmol of 1. Compound 9d
To an oven-dried round-bottomed flask under an atmos-
phere of N2 containing 3 mL of freshly distilled THF was
added 0.5 mmol of 7a followed by 10 mg each of Pd/C and
Pd(OH)2. The reaction vessel was purged with H2(g) and
maintained under an atmosphere of H2(g) for 2 h while stir-
ring vigorously. Upon consumption of the starting material
as monitored by TLC (60:40 EtOAc:Hex (v/v)), the reaction
mixture was purged with N2 and cooled in an ice bath, and
1.0 mmol of NaH (60% in mineral oil) was added. The mix-
ture was stirred for 30 min at RT followed by the addition
of 0.2 mmol of 1. The reaction mixture was subsequently re-
fluxed overnight. Upon consumption of the starting material,
the reaction was filtered through celite and the THF was re-
moved under reduced pressure. The product was dissolved
in 30 mL of CH2Cl2 and washed with 30 mL of H2O, and
the aqueous layer was further extracted with 30 mL of
CH2Cl2. The combined organic layers were washed with
30 mL of brine, dried over Na2SO4, and concentrated. The
product was purified by PTLC (60:40 EtOAc:Hex (v/v)) to
yield 21 mg 9a (41%). 1H NMR (CDCl3, 400 MHz) d:
1
was obtained in a 35% yield (25 mg). H NMR (CDCl3,
3
400 MHz) d: 7.08–7.04 (m, 2H), 4.45 (t, JHH = 6.6 Hz,
2
3
2H), 4.45 (dt, JHF = 47.6 Hz, JHH = 6.2 Hz, 2H), 3.47–344
(m, 2H), 2.61–2.56 (m, 2H), 2.48–2.43 (m, 2H), 2.47 (s,
3H), 1.89–1.81 (m, 2H), 1.76–1.62 (m, 2H), 1.51–1.40 (m,
5H). 19F NMR (CDCl3, 376 MHz) d: –218.62 (tt, JHF
=
2
3
47.5 Hz, JHF = 25.2 Hz). HR-MS calcd. for C15H25FN3OS
[M + 1]: 314.1697; found: 314.1693. EA calcd.: C 57.48, H
7.72, N 13.41; found: C 57.69, H 7.65, N 13.17.
3-(2-(2-Fluoroethoxy)ethoxy)-4-(1-methyl-1,2,5,6-
tetrahydropyridin-3-yl)-1,2,5-thiadiazole (9e)
Compound 9e was prepared in an analogous manner to
that of 9a, where 0.4 mmol of 7e was used followed by
1.4 mmol of 60% NaH and 0.23 mmol of 1. Compound 9e
1
was obtained in a 45% yield (30 mg). H NMR (CDCl3,
400 MHz) d: 7.12–7.07 (m, 1H), 4.64–4.61 (m, 2H), 4.58
2
(dm, JHF = 47.6 Hz, 2H), 3.96–3.92 (m, 2H), 3.79 (dm,
3JHF = 29.4 Hz, 2H), 3.47–3.44 (m, 2H), 2.60–2.55 (m, 2H),
2
7.04–6.99 (m, 1H), 4.63 (dm, JHF = 47.0 Hz, 2H), 4.61 (t,
2.49–2.43 (m, 2H), 2.46 (s, 3H). 19F NMR (CDCl3,
3JHH = 6.2 Hz, 2H), 3.47–3.43 (m, 2H), 2.60–2.55 (m, 2H),
2
3
376 MHz) d: –223.51 (tt, JHF = 47.7 Hz, JHF = 28.9 Hz).
HR-MS calcd. for C12H19FN3O2S [M + 1]: 288.1177; found:
288.1173. EA calcd.: C 50.16, H 6.361, N 14.62; found: C
50.25, H 6.44, N 14.40.
3
2.48–2.42 (m, 2H), 2.46 (s, 3H), 2.25 (dm, JHF = 25.6 Hz,
2
2H). 19F NMR (CDCl3, 376 MHz) d: –222.38 (tt, JHF
=
3
47.0 Hz, JHF = 25.8 Hz). HR-MS calcd. for C11H17FN3OS
[M + 1]: 258.1071; found: 258.1068. EA calcd.: C 51.34, H
6.27, N 16.33; found: C 51.64, H 6.27, N 15.84.
3-(2-(2-(2-Fluoroethoxy)ethoxy)ethoxy)-4-(1-methyl-
1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazole (9f)
Compound 9f was prepared in an analogous manner to
that of 9a, where 0.4 mmol of 7f was used followed by
1.4 mmol of 60% NaH and 0.23 mmol of 1. Compound 9f
3-(5-Fluoropentyloxy)-4-(1-methyl-1,2,5,6-
tetrahydropyridin-3-yl)-1,2,5-thiadiazole (9b)
Compound 9b was prepared in an analogous manner to
that of 9a, where 0.4 mmol of 7b was used followed by
1.4 mmol of 60% NaH and 0.23 mmol of 1. Compound 9b
1
was obtained in a 62% yield (46 mg). H NMR (CDCl3,
400 MHz) d: 7.11–7.07 (m, 1H), 4.63–4.60 (m, 3H), 4.51–
4.48 (m, 1H), 3.93–3.90 (m, 2H), 3.79–3.77 (m, 1H), 3.74–
3.68 (m, 5H), 3.47–3.45 (m, 2H), 3.60–3.56 (m, 2H), 2.47–
2.43 (m, 2H), 2.46 (s, 3H). 19F NMR (CDCl3, 376 MHz)
1
was obtained in a 29% yield (19 mg). H NMR (CDCl3,
2
400 MHz) d: 7.07–7.03 (m, 1H), 4.48 (dt, JHF = 46.9 Hz,
3
3JHH = 6.1 Hz, 2H), 4.47 (t, JHH = 6.5 Hz, 2H), 3.50–3.47
2
3
(m, 2H), 2.64–2.59 (m, 2H), 2.50–2.44 (m, 2H), 2.49 (s,
d: –223.30 (tt, JHF = 47.7 Hz, JHF = 29.5 Hz). HR-MS
calcd. for C14H23FN3O3S [M + 1]: 332.1439; found:
332.1434. EA calcd.: C 50.74, H 6.69, N 12.68; found: C
50.87, H 6.75, N 12.86.
3H), 1.94–1.86 (m, 2H), 1.85–1.72 (m, 2H), 1.64–1.56 (m,
2
2H). 19F NMR (CDCl3, 376 MHz) d: –219.18 (tt, JHF
=
3
47.1 Hz, JHF = 25.4 Hz). HR-MS calcd. for C13H21FN3OS
[M + 1]: 286.1384; found: 286.1380. EA calcd.: C 54.71, H
7.06, N 14.72; found: C 54.90, H 6.87, N 14.79.
3-(Hexyloxy)-4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-
1,2,5-thiadiazole (10)
3-(6-Fluorohexyloxy)-4-(1-methyl-1,2,5,6-
tetrahydropyridin-3-yl)-1,2,5-thiadiazole (9c)
To an oven-dried round-bottomed flask, 71 mg
(0.7 mmol) of 1-hexanol was added to 3 mL of freshly dis-
tilled THF. To the reaction mixture was added 34 mg
(1.4 mmol) of 95% NaH, and the mixture was allowed to
stir at RT for 30 min. Compound 1 (0.35 mmol) was subse-
quently added and the reaction was refluxed overnight. The
reaction was diluted with 30 mL of H2O and washed with
Compound 9c was prepared in an analogous manner to
that of 9a, where 0.4 mmol of 7c was used followed by
1.4 mmol of 60% NaH and 0.23 mmol of 1. Compound 9c
1
was obtained in a 39% yield (27 mg). H NMR (CDCl3,
3
400 MHz) d: 7.07–7.03 (m, 1H), 4.46 (t, JHH = 6.9 Hz,
Published by NRC Research Press