Mar-Apr 2006
N-Acyl and N-Alkoxycarbonyl Derivatives of 1H-1,2,3-Triazolo[4,5-c]pyridine
421
(
100 mg, 0.47-0.66 mmol), tetrafluoroboric acid (43-63 mg, 1.05
%), 150 (13), 135 (53), 119 (15), 107 (100), 91 (12), 80 (26);
HRMS: calcd for C H N O ; 178.04908, observed 178.04917.
equivalent) and iso-amyl nitrite (58-81 mg, 1.05 equiv.) in
7
6
4
2
ethanol (1 ml) was stirred at 0 °C for approx. 15 minutes. The
product 1a-e were afforded as tetrafluoroborates, pure by H
1
1-Ethoxycarbonyl-1H-1,2,3-triazolo[4,5-c]pyridine (1d)
Tetrafluoroborate.
nmr. The acyl (1a,b) and the tert-butyl carbamate (BOC, 1e)
products easily hydrolyzed into the non-derivatised triazolo-
pyridine 1 by extraction and isolation and were therefore
prepared in situ (see below) and used directly in the next step
without further purification. Only methoxy- and ethoxycarbonyl-
triazolopyridine (1c,d) were fully characterized as their
respective tetrafluoroborates, while the “free” methoxy, ethoxy
and tert-butoxy triazolopyridine derivatives (1c,d,e) were
characterized after preparation by acetic acid and iso-amyl
nitrite [6]. For synthetic use, all compounds 1a-e were prepared
in situ and reacted directly with the amines, see general N-
acylation/N-alkoxycarbonylation procedure below.
1
This compound was prepared from 7d, pure by H nmr
(quantitative conversion, > 95 % isolated yield); mp 143.5-144.5
°C (pentane); ir (potassium bromide) 3066w, 1771s, 1635s,
1613s, 1558m, 1498m, 1323s, 1109s, 1070s, 1018s, 958m, 838m,
786s, 713m cm ; H nmr (300 MHz, d -dimethyl sulfoxide): ꢀ
1.60 (t, J 7.1, 3H), 4.75 (q, J 7.1, 2H), 8.30 (d, J 6.1, 1H, H-2),
8.88 (d, J 6.1, 1H, H-6), 9.85 (s, 1H, H-5); C nmr (75 MHz, d6-
dimethyl sulfoxide): ꢀ 13.9, 65.9, 109.6, 136.8, 142.2, 143.0,
145.1, 147.5; F nmr (376 MHz, d -dimethyl sulfoxide) ꢀ -148.1.
-1
1
6
1
3
1
9
6
Anal. Calcd. for C H BF N O : C, 34,32; H, 3,24; N, 20,01.
8
9
4
4
2
Found: C, 33.98; H, 3,23; N, 19,75.
1
-Acetyl-1H-1,2,3-triazolo[4,5-c]pyridine (1a) Tetrafluoroborate.
1-Ethoxycarbonyl-1H-1,2,3-triazolo[4,5-c]pyridine (1d).
Free 1d was prepared according to literature [6] to give 96 %
1
This compound was prepared from 7a, pure by H nmr
1
1
(quantitative conversion); H nmr (300 MHz, d -dimethyl
yield, pure by H nmr; mp 170-171 °C; ir (potassium bromide)
6
sulfoxide): ꢀ 3.01 (s, 3H), 8.46 (d, J 6.2, 1H, H-5), 8.60 (d, J
3159m, 2989m, 1790s, 1710s, 1593m, 1514m, 1477m, 1401w,
13
-1 1
6
.2, 1H, H-6), 9.86 (s, 1H, H-2); C nmr (100 MHz, d -dimethyl
1366m, 1319w, 1231s, 1062s, 837w, 795w, 772w cm ; H nmr
(300 MHz, deuteriochloroform): ꢀ 1.61 (t, J 7.1, 3H), 4.74 (q, J
7.1, 2H), 8.04 (dd, J 1.0, 5.7, 1H, H-2), 8.78 (d, J 5.7, 1H, H-6),
6
1
9
sulfoxide): ꢀ 12.6, 111.1, 135.8, 139.7, 142.4, 143.1, 170.0. F
nmr (376 MHz, d -dimethyl sulfoxide) ꢀ -148.8.
6
1
3
9
.56 (d, J 1.0, 1H, H-5); C nmr (75 MHz, deuteriochloroform):
1-Benzoyl-1H-1,2,3-triazolo[4,5-c]pyridine (1b) Tetrafluoroborate.
ꢀ
13.8, 65.5, 107.7, 135.6, 142.4, 144.2, 147.6, 147.9; ms: m/z
1
+
This compound was prepared from 7b, pure by H nmr
192 (M , 25 %), 164 (6), 136 (100), 120 (54), 105 (2), 92 (61),
80 (12); HRMS: calcd for C H N O ; 192.0647 observed
1
(quantitative conversion);
H nmr (400 MHz, deuterio-
8
8
4
2
chloroform): ꢀ 7.38 (m, 2H, Ph-H), 7.52 (m, 1H, Ph-H), 7.86 (d,
192.06419.
J 7.2, 2H), 8.33 (d, J 6.8, 1H, H-5), 8.60 (d, J 6.8, 1H, H-6), 9.81
1
3
1-tert-Butoxycarbonyl-1H-1,2,3-triazolo[4,5-c]pyridine (1e)
Tetrafluoroborate.
(
1
s, 1H, H-2); C nmr (100 MHz, deuteriochloroform): ꢀ 110.7,
28.4, 129.0, 129.3, 133.5, 135.1, 138.5, 140.0, 140.6, 169.8. F
1
9
1
nmr (376 MHz, d -dimethyl sulfoxide) ꢀ -148.3.
This compound was prepared from 7e, pure by H nmr
6
1
(
quantitative conversion, > 95 % isolated yield); H nmr (300
1
-Methoxycarbonyl-1H-1,2,3-triazolo[4,5-c]pyridine (1c)
MHz, d -dimethyl sulfoxide): ꢀ 1.72 (s, 9H), 8.35 (d, J 6.4, 1H,
6
Tetrafluoroborate.
13
H-5), 8.84 (d, J 6.4, 1H, H-6), 9.97 (s, 1H, H-2); C nmr (100
1
This compound was prepared from 7c, pure by H nmr
quantitative conversion). 1c tetrafluoroborate precipitated
MHz, deuteriochloroform): ꢀ 27.7, 89.9, 111.8, 135.9, 141.7,
1
9
(
142.8, 146.0, 149.4; F nmr (376 MHz, d -dimethyl sulfoxide) ꢀ
6
quantitatively from the reaction solution and could be
recrystallized (> 95 %); mp 156-157 °C (acetone). ir (potassium
bromide) 3274s, 3147m, 3087m, 2969w, 1800s, 1644s, 1618m,
-148.9.
1
-tert-Butoxycarbonyl-1H-1,2,3-triazolo[4,5-c]pyridine (1e).
Free 1e was prepared from 7e and nitrosonium tetrafluoro-
-
1
1
552m, 1474s, 1437m, 1369m, 1253s, 1090s, 943m, 911s cm ;
1
H nmr (400 MHz, d -dimethyl sulfoxide): ꢀ 4.30 (s, 3H), 8.38
borate and added triethyl amine to give 81 % yield of free 1e,
pure by H nmr; mp 87-88 °C; ir (potassium bromide) 3004m,
6
1
(d, J 6.1, 1H, H-5), 8.89 (d, J 6.1, 1H, H-6), 9.89 (s, 1H, H-2);
correspondingly in d -acetone: ꢀ 4.37 (s, 3H), 8.88 (d, J 6.8,
2989m, 1782m, 1709s, 1601w, 1364s, 1321w, 1255m, 1222m,
1152m, 1092m, 1040m, 930w, 828w cm ; H nmr (400 MHz,
6
1
3
-1
1
1
H, H-5), 9.25 (d, J 6.8, 1H, H-6), 10.33 (s, 1H, H-2); C nmr
(
1
ꢀ
75 MHz, d -dimethyl sulfoxide): ꢀ 56.0, 110.6, 135.8, 140.6,
deuteriochloroform): ꢀ 1.79 (s, 9H), 7.98 (dd, J 0.8, 5.6, 1H, H-
2), 8.74 (d, J 5.6, 1H, H-6), 9.52 (s, 1H, H-5); C nmr (100
MHz, deuteriochloroform): ꢀ 27.9, 88.0, 108.1, 135.9, 142.9,
6
19
13
42.4, 145.4, 148.2; F nmr (376 MHz, d -dimethyl sulfoxide)
6
-148.5.
Anal. Calcd. for C H BF N O : C, 31.61; H, 2.65; N, 21.07.
144.5, 146.5, 147.7.
7
7
4
4
2
Found: C, 31.67; H, 2.54; N, 20.85.
1
-Methylsulfonyl-1H-1,2,3-triazolo[4,5-c]pyridine (1-Ms).
This compound was made according to the procedure for N-
1
-Methoxycarbonyl-1H-1,2,3-triazolo[4,5-c]pyridine (1c).
Free 1c was prepared according to literature [6] to give 92 %
yield, pure by H nmr; mp 139-140 °C; ir (potassium bromide)
(1-methanesulfonyl)benzotriazole (3-Ms) [11] in 30 % yield.
1
The compound was unstable and could not be isolated for full
1
3
1
106m, 3000w, 2972w, 1794s, 1626m, 1475m, 1448m, 1377s,
330m, 1256s, 1213s, 1181s, 1062s, 922m, 844m, 759m, 587m
characterization; H nmr (300 MHz, deuteriochloroform): 3.54
(s, 3H), 7.86 (dd, J 5.80, 1H), 8.69 (d, J 5.80, 1H), 9.47 (d, J 1.0,
-
1
1
13
cm ; H nmr (300 MHz, deuteriochloroform): ꢀ 4.28 (s, 3H),
1H); C nmr (75 MHz, deuteriochloroform): ꢀ 43.1, 106.6,
8
1
1
.03 (dd, J 1.1, 5.7, 1H, H-2), 8.78 (d, J 5.7, 1H, H-6), 9.60 (d, J
135.8, 141.9, 144.8, 147.9. IR (film): 3651, 3422, 2254, 1598,
1
3
-1
.1, 1H, H-5); C nmr (75 MHz, d -dimethyl sulfoxide): ꢀ 56.2,
1386, 1255, 1194, 1179, 967, 734 cm ; ir (potassium bromide)
6
+
-1
08.4, 136.5, 143.3, 145.1, 148.6, 149.3; ms: m/z 178 (M , 51
1598w, 1386m, 1193s, 1179s cm ;