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The Journal of Organic Chemistry
(dd, J = 4.7, 0.8 Hz, 1H), 7.31 (d, J = 4.4 Hz,
1H NMR (500 MHz, DMSO-d6): δ 8.33 (d, J
1
2
3
4
5
6
7
8
4H), 7.23 (h, J = 4.0 Hz, 1H), 3.59 – 3.53 (m,
2H), 3.06 – 3.00 (m, 2H). 13C{1H} NMR (126
MHz, DMSO-d6): δ 152.2, 142.7, 139.9, 138.1,
128.7, 128.6, 128.4, 126.4, 114.3, 34.4, 29.4.
HRMS (ESI/FTICR) m/z: [M + Na]+ calcd
for C13H12N4SNa 279.0675; found 279.0671.
N-Phenethyl-[1,2,4]triazolo[4,3-a]pyrazin-8-
amine (30). Preparation 1: General Proce-
dure E was applied using 25 (104 mg, 0.654
mmol) and 2-phenylethan-1-amine (244 mg,
2.01 mmol, 3.0 equiv.) to give 30 as an off-
white solid (135 mg, 0.564 mmol, 84%). Prepa-
ration 2: General Procedure E was applied us-
ing 45a (100 mg, 0.649 mmol, 1.0 equiv.) and
2-phenylethan-1-amine (235 mg, 1.95 mmol, 3.0
equiv.) to give 30 as an off-white solid (102 mg,
0.424 mmol, 65%). mp 191–193 °C (decomp.).
1H NMR (500 MHz, DMSO-d6): δ 9.19 (s, 1H),
8.16 (t, J = 5.8 Hz, 1H), 7.74 (d, J = 4.7 Hz,
1H), 7.32 – 7.23 (m, 5H), 7.23 – 7.15 (m, 1H),
3.71 (q, J = 6.9 Hz, 2H), 2.99 – 2.92 (m, 2H).
13C{1H} NMR (126 MHz, DMSO-d6): δ 147.4,
139.5, 138.6, 138.1, 129.1, 128.6, 128.3, 126.0,
107.2, 41.6, 34.5. HRMS (ESI/FTICR) m/z:
[M + H]+ calcd for C13H14N5 240.1244; found
240.1241.
8-Phenethoxy-3-phenyl-[1,2,4]triazolo[4,3-
a]pyrazine (31). General Procedure D was
applied using 26 (115 mg, 0.499 mmol, 1.0
equiv.) and 2-phenylethan-1-ol (60.9 mg, 0.499
mmol, 1.0 equiv.) to give 31 as a white solid
(91.0 mg, 0.288 mmol, 58%). mp 145–147 °C.
1H NMR (500 MHz, DMSO-d6): δ 8.19 (d, J
= 4.9 Hz, 1H), 7.94 – 7.88 (m, 2H), 7.68 –
7.59 (m, 3H), 7.47 (d, J = 4.9 Hz, 1H), 7.41
– 7.29 (m, 4H), 7.24 (t, J = 7.3 Hz, 1H), 4.76
(t, J = 6.8 Hz, 2H), 3.19 (t, J = 6.9 Hz, 2H).
13C{1H} NMR (126 MHz, DMSO-d6): δ 153.2,
148.0, 139.7, 138.0, 130.5, 129.3, 129.0, 128.4,
128.1, 127.4, 126.4, 125.9, 112.1, 67.4, 34.2.
HRMS (ESI/FTICR) m/z: [M + Na]+ calcd
for C19H16N4ONa 339.1216; found 339.1217.
8-(Phenethylthio)-3-phenyl-[1,2,4]triazolo-
[4,3-a]pyrazine (32). General Procedure D was
applied using 26 (107 mg, 0.464 mmol) and
2-phenylethane-1-thiol (65.1 mg, 0.464 mmol,
1.0 equiv.) to give 32 as an off-white solid
(145 mg, 0.440 mmol, 94%). mp 154–156 °C.
= 4.8 Hz, 1H), 7.97 – 7.88 (m, 2H), 7.83 (d, J
= 4.8 Hz, 1H), 7.69 – 7.59 (m, 3H), 7.33 (d,
J = 5.0 Hz, 4H), 7.24 (ddd, J = 8.8, 5.3, 3.5
Hz, 1H), 3.63 – 3.56 (m, 2H), 3.09 – 3.02 (m,
2H). 13C{1H} NMR (126 MHz, DMSO-d6): δ
153.0, 147.6, 143.8, 140.0, 130.5, 129.5, 129.3,
128.6, 128.4, 128.2, 126.4, 125.7, 113.2, 34.4,
29.4. HRMS (ESI/FTICR) m/z: [M + H]+
calcd for C19H17N4S 333.1168; found 333.1164.
N-Phenethyl-3-phenyl-[1,2,4]triazolo[4,3-
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
a]pyrazin-8-amine (33). General Procedure E
was applied using 26 (102 mg, 0.442 mmol) and
2-phenylethan-1-amine (161 mg, 1.33 mmol, 3.0
equiv.) to give 33 (120 mg, 0.381 mmol, 86%).
1
mp 206–209 °C. H NMR (500 MHz, DMSO-
d6): δ 8.27 (t, J = 5.7 Hz, 1H), 7.92 – 7.86 (m,
2H), 7.75 (d, J = 4.8 Hz, 1H), 7.67 – 7.57 (m,
3H), 7.36 (d, J = 4.8 Hz, 1H), 7.34 – 7.25 (m,
4H), 7.25 – 7.17 (m, 1H), 3.79 – 3.71 (m, 2H),
3.02 – 2.95 (m, 2H). 13C{1H} NMR (126 MHz,
DMSO-d6): δ 147.9, 147.7, 139.6, 139.5, 130.2,
130.2, 129.3, 128.7, 128.3, 128.0, 126.3, 126.1,
106.0, 41.6, 34.5. HRMS (ESI/FTICR) m/z:
[M + H]+ calcd for C19H18N5 316.1557; found
316.1553.
3-(4-Nitrophenyl)-8-phenethoxy-[1,2,4]tria-
zolo[4,3-a]pyrazine (34). Preparation 1: Gen-
eral Procedure D was applied using 27 (113 mg,
0.410 mmol, 1.0 equiv.) and 2-phenylethan-1-ol
(50.1 mg, 0.410 mmol, 1.0 equiv.) to give 34
as a yellow solid (125 mg, 0.346 mmol, 84%).
Preparation 2: isolated from the same reaction
as for 46e preparation 1: fractions correspond
to the first peak were evaporated to give 34 as
a yellow solid (2.05 mg, 5.51 µmol, 2%). mp
238–240 °C (decomp.). 1H NMR (500 MHz,
DMSO-d6): δ 8.45 (d, J = 8.3 Hz, 2H), 8.32
(d, J = 4.9 Hz, 1H), 8.24 (d, J = 8.4 Hz, 2H),
7.56 (d, J = 4.9 Hz, 1H), 7.38 (d, J = 7.6 Hz,
2H), 7.33 (t, J = 7.5 Hz, 2H), 7.24 (t, J =
7.2 Hz, 1H), 4.79 (t, J = 6.8 Hz, 2H), 3.20 (t,
J = 6.8 Hz, 2H). 13C{1H} NMR (126 MHz,
DMSO-d6): δ 153.2, 148.2, 146.5, 140.1, 137.9,
132.0, 129.4, 128.9, 128.4, 127.9, 126.4, 124.3,
112.4, 67.5, 34.2. HRMS (ESI/FTICR) m/z:
[M + H]+ calcd for C19H16N5O3 362.1248; found
362.1246.
3-(4-Nitrophenyl)-8-(phenethylthio)-[1,2,4]-
ACS Paragon Plus Environment
13