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doi.org/10.1002/cmdc.202100431
ChemMedChem
Htetrahydronaphthoyl), 5.06 (t, J=6.3 Hz, 1H, 1-Htetrahydronaphthoyl), 2.86–2.72
(m, 2H, 4-Htetrahydronaphthoyl), 2.25–2.16 (m, 1H, 2a-Htetrahydronaphthoyl), 2.15–
2.08 (m, 1H, 2b-Htetrahydronaphthoyl), 1.93–1.85 (m, 1H, 3a-Htetrahydronaphthoyl),
1.81–1.74 (m, 1H, 3b-Htetrahydronaphthoyl). 13C-NMR (151 MHz, DMSO-d6,
299 K): δ (in ppm)=175.6 (1 C, C=O), 158.1 (1 C, 5-Ctriazolyl), 157.5
(1 C, 3-Ctriazolyl), 145.7 (1 C, 5-Cpyrazine), 144.8 (1 C, 6-Cpyrazine), 144.6 (1 C,
2-Cpyrazine), 143.4 (1 C, 3-Cpyrazine), 137.5 (1 C, 4a-Ctetrahydronaphthoyl), 133.0
(1 C, 8a-Ctetrahydronaphthoyl), 129.4 (1 C, 8-Ctetrahydronaphthoyl), 129.2 (1 C, 5-
2H, 4-Htetrahydronaphthoyl), 2.14–2.03 (m, 2H, 2-Htetrahydronaphthoyl), 1.92–1.84
(m, 1H, 3a-Htetrahydronaphtoyl), 1.78–1.67 (m, 1H, 3b-Htetrahydronaphthoyl), 1.27
(s, 9H, -C(CH3)3). 13C-NMR (151 MHz, DMSO-d6, 299 K): δ (in ppm)=
175.3 (1 C, C=O), 170.2 (1 C, 3-Ctriazolyl), 157.5 (1 C, 5-Ctriazolyl), 137.5
(1 C, 4a-Ctetrahydronaphthoyl), 133.2 (1 C, 8a-Ctetrahydronaphthoyl), 129.1 (1 C, 8-
Ctetrahydronaphthoyl), 129.1 (1 C, 5-Ctetrahydronaphthoyl), 126.7 (1 C, 6-/7-
C
C
tetrahydronaphthoyl), 125.7 (1 C, 6-/7-Ctetrahydronaphthoyl), 43.2 (1 C, 1-
tetrahydronaphthoyl), 32.5 (1 C, -C-(CH3)3), 28.6 (3 C, -C-(CH3)3), 26.1 (1 C,
C
C
tetrahydronaphthoyl), 126.8 (1 C, 6-/7-Ctetrahydronaphthoyl), 125.8 (1 C, 6-/7-
tetrahydronaphthoyl), 43.3 (1 C, 1-Ctetrahydronaphthoyl), 28.6 (1 C, 4-
3a-Ctetrahydronaphthoyl), 20.0 (1 C, 3b-Ctetrahydronaphthoyl). IR (neat): v˜ [cmÀ 1]=
3433, 3020, 2970, 1709, 1643, 1543, 1450, 1373, 1273, 1196, 991,
745. HRMS (APCI): m/z=299.1866 calculated for C17H23N4O+ [M+
H]+, found: 299.1863. HPLC: tR =20.8 min, purity: 96.2%.
Ctetrahydronaphthoyl), 26.3 (1 C, 2-Ctetrahydronaphthoyl), 19.9 (1 C, 3-
C
tetrahydronaphthoyl). IR (neat): v˜ [cmÀ 1]=3460, 3062, 2932, 1709, 1632,
1543, 1439, 1366, 1146, 1015, 741. HRMS (APCI): m/z=321.1458
calculated for C17H17N6O+ [M+H]+, found: 321.1457. HPLC: tR =
19.0 min, purity: 96.1%.
(S)-(5-Amino-3-(4-fluorophenyl)-1H-1,2,4-triazol-1-yl)(1,2,3,4-tetrahy-
dronaphthalen-1-yl)-methanone (33f). Compound 15l (80 mg,
449 μmol, 1.0 eq.), (S)-1,2,3,4-tetrahydronaphthalene-1-carboxylic
acid (79 mg, 449 μmol, 1.0 eq.), DMAP (110 mg, 898 μmol, 2.0 eq.)
and EDCI·HCl (172 mg, 898 μmol, 2.0 eq.) were dissolved in DMF
(S)-(5-Amino-3-(2-methyl-6-(thiophen-2-yl)pyridin-3-yl)-1H-1,2,4-tria-
zol-1-yl)(1,2,3,4-tetrahydro-naphthalen-1-yl)methanone (33d). Com-
pound 29f (80 mg, 311 μmol, 1.0 eq.), (S)-1,2,3,4-tetrahydronaph-
thalene-1-carboxylic acid (55 mg, 311 μmol, 1.0 eq.), DMAP (76 mg,
622 μmol, 2.0 eq.) and EDCI·HCl (119 mg, 622 μmol, 2.0 eq.) were
°
(7 mL, dry) and pyridine (2 mL, dry) at 0 C under nitrogen
°
atmosphere. The solution was stirred at 0 C for 1 h and then at r.t.
for 4 h. The reaction mixture was poured into cold H2O and stored
°
°
dissolved in DMF (7 mL, dry) and pyridine (2 mL, dry) at 0 C under
at 4 C for 15 min. The formed precipitate was filtered off and
washed thoroughly with H2O. The remaining solid was dried in
vacuo, the product was obtained as a colourless solid (140 mg,
°
nitrogen atmosphere. The solution was stirred at 0 C for 1 h and
then at r.t. for 4 h. The reaction mixture was poured into cold H2O
°
°
and stored at 4 C for 15 min. The formed precipitate was filtered
off and washed with H2O and Et2O. The remaining solid was dried
in vacuo, the product was obtained as a colourless solid (113 mg,
416 μmol, 93%). M.p.=204.5 C. TLC: Rf =0.49 (DCM/MeOH=20/1).
1H-NMR (600 MHz, DMSO-d6, 299 K): δ (in ppm)=8.08–8.02 (m, 2H,
2-/6-Hfluorophenyl), 7.72 (s, 2H, À NH2), 7.35–7.30 (m, 2H, 3-/5-Hfluorophenyl),
7.20–7.13 (m, 2H, 5-Htetrahydronaphthoyl, 6-/7-Htetrahydronaphthoyl), 7.12–7.06
(m, 2H, 8-Htetrahydronaphthoyl, 6-/7-Htetrahydronaphthoyl), 5.04 (t, J=6.4 Hz, 1H,
1-Htetrahydronaphthoyl), 2.85–2.74 (m, 2H, 4-Htetrahydronaphthoyl), 2.22–2.16 (m,
1H, 2a-Htetrahydronaphthoyl), 2.15–2.08 (m, 1H, 2b-Htetrahydronaphthoyl), 1.94–
1.86 (m, 1H, 3a-Htetrahydronaphthoyl), 1.80–1.72 (m, 1H, 3b-Htetrahydronaphthoyl).
13C-NMR (151 MHz, DMSO-d6, 299 K): δ (in ppm)=175.4 (1 C, C=O),
163.3 (d, JC,F =247.4 Hz, 1 C, 4-Cfluorophenyl), 158.8 (1 C, 3-Ctriazolyl), 158.0
(1 C, 5-Ctriazolyl), 137.5 (1 C, 4a-Ctetrahydronaphthoyl), 133.1 (1 C, 8a-
°
272 μmol, 87%). M.p.=176.5 C. TLC: Rf =0.38 (DCM/MeOH=20/1).
1H-NMR (600 MHz, DMSO-d6, 299 K): δ (in ppm)=8.31 (d, J=8.2 Hz,
1H, 4-Hpyridyl), 7.88 (d, J=8.2 Hz, 1H, 5-Hpyridyl), 7.85 (d, J=3.7 Hz, 1H,
3-/5-Hthiophenyl), 7.73 (s, 2H, -NH2), 7.68 (d, J=5.0 Hz, 1H, 3-/5-
H
thiophenyl), 7.19 (dd, J=5.0, 3.7 Hz, 1H, 4-Hthiophenyl), 7.18–7.14 (m, 2H,
5-Htetrahydronaphthoyl
,
6-/7-Htetrahydronaphthoyl), 7.14–7.09 (m, 2H, 8-
Htetrahydronaphthoyl
,
6-/7-Htetrahydronaphthoyl), 5.02 (t, J=6.3 Hz, 1H, 1-
H
H
tetrahydronaphthoyl), 2.84 (s, 3H, À CH3), 2.83–2.73 (m, 2H, 4-
tetrahydronaphthoyl), 2.25–2.14 (m, 2H, 2-Htetrahydronaphthoyl), 1.94–1.86 (m,
C
C
tetrahydronaphthoyl), 129.3 (1 C, 8-Ctetrahydronaphthoyl), 129.2 (1 C, 5-
tetrahydronaphthoyl), 128.8 (d, JC,F =8.7 Hz, 2 C, 2-/6-Cfluorophenyl), 126.8 (1 C,
1H, 3a-Htetrahydronaphthoyl), 1.81–1.73 (m, 1H, 3b-Htetrahydronaphthoyl). 13C-
NMR (151 MHz, DMSO-d6, 299 K): δ (in ppm)=175.4 (1 C, C=O),
158.7 (1 C, 3-Ctriazolyl), 157.3 (1 C, 5-Ctriazolyl), 156.5 (1 C, 2-Cpyridyl), 151.4
(1 C, 6-Cpyridyl), 144.0 (1 C, 2-Cthiophenyl), 137.7 (1 C, 4-Cpyridyl), 137.5 (1 C,
4a-Ctetrahydronaphthoyl), 133.1 (1 C, 8a-Ctetrahydronaphthoyl), 129.3 (1 C, 8-
Ctetrahydronaphthoyl), 129.2 (1 C, 5-Ctetrahydronaphthoyl), 129.1 (1 C, 3-/5-
6-/7-Ctetrahydronaphthoyl), 126.7 (d, JC,F =2.9 Hz, 1 C, 1-Cfluorophenyl), 125.8
(1 C, 6-/7-Ctetrahydronaphthoyl), 115.8 (d, JC,F =22.0 Hz, 2 C, 3-/5-Cfluorophenyl),
43.3 (1 C, 1-Ctetrahydronaphthoyl), 28.6 (1 C, 4-Ctetrahydronaphthoyl), 26.2 (1 C, 2-
C
tetrahydronaphthoyl), 20.0 (1 C, 3-Ctetrahydronaphthoyl). IR (neat): v˜ [cmÀ 1]=
3426, 3024, 2924, 1717, 1643, 1543, 1126, 991, 841, 741, 610. HMRS
(APCI): m/z=337.1459 calculated for C19H18FN4O+ [M+H]+, found:
337.1459. HPLC: tR =22.4 min, purity: 98.3%.
C
thiophenyl), 128.5 (1 C, 4-Cthiophenyl), 126.8 (1 C, 6-/7-Ctetrahydronaphthoyl),
125.9 (1 C, 3-/5-Cthiophenyl), 125.8 (1 C, 6-/7-Ctetrahydronaphthoyl), 122.9 (1 C,
3-Cpyridyl), 116.0 (5-Cpyridyl), 43.7 (1 C, 1-Ctetrahydronaphthoyl), 28.6 (1 C, 4-
Ctetrahydronaphthoyl), 26.2 (1 C, 2-Ctetrahydronaphthoyl), 25.2 (1 C, À CH3), 20.1
(1 C, 3-Ctetrahydronaphthoyl). IR (neat): v˜ [cmÀ 1]=3453, 3017, 2932, 1709,
1647, 1574, 1466, 1369, 1319, 1153, 991, 745. HRMS (APCI): m/z=
416.1540 calculated for C23H22N5OS+ [M+H]+, found: 416.1579.
HPLC: tR =22.7 min, purity: 95.3%.
(S)-(5-Amino-3-(quinolin-2-yl)-1H-1,2,4-triazol-1-yl)(1,2,3,4-tetrahydro-
naphthalen-1-yl)-methanone (33g). Compound 15k (100 mg,
473 μmol, 1.0 eq.), (S)-1,2,3,4-tetrahydronaphthalene-1-carboxylic
acid (83 mg, 473 μmol, 1.0 eq.), DMAP (116 mg, 947 μmol, 2.0 eq.)
and EDCI·HCl (182 mg, 947 μmol, 2.0 eq.) were dissolved in DMF
(7 mL) and pyridine (2 mL, both dry) under nitrogen atmosphere at
°
°
(S)-(5-Amino-3-(tert-butyl)-1H-1,2,4-triazol-1-yl)(1,2,3,4-tetrahydro-
naphthalen-1-yl)methanone (33e). Compound 15h (80 mg,
571 μmol, 1.0 eq.), (S)-1,2,3,4-tetrahydronaphthalene-1-carboxylic
acid (101 mg, 571 μmol, 1.0 eq.), DMAP (139 mg, 1.14 mmol,
2.0 eq.) and EDCI·HCl (219 mg, 1.14 mmol, 2.0 eq.) were dissolved in
0 C. The solution was stirred at 0 C for 1 h and then at r.t. for 4 h.
°
The reaction mixture was poured into cold H2O and stored at 4 C
for 15 min. The formed precipitate was washed thoroughly with
H2O, the remaining product was dried in vacuo. The product was
obtained as a slight brown solid (80 mg, 216 μmol, 44%). M.p. =
206.5 C. TLC: Rf =0.48 (DCM/MeOH=20/1). 1H-NMR (600 MHz,
°
°
DMF (7 mL, dry), and pyridine (2 mL, dry) at 0 C under nitrogen
°
atmosphere. The solution was stirred at 0 C for 1 h and then at r.t.
for 4 h. The reaction mixture was poured into cold H2O and stored
DMSO-d6, 299 K): δ (in ppm)=8.51 (d, J=8.5 Hz, 1H, 4-Hquinoline), 8.22
(d, J=8.5 Hz, 1H, 3-Hquinoline), 8.13 (d, J=8.4 Hz, 1H, 8-Hquinoline), 8.05
(d, J=8.0 Hz, 1H, 5-Hquinoline), 7.83 (t, J=8.4, 7.4 Hz, 1H, 7-Hquinoline),
7.78 (s, 2H, À NH2), 7.67 (d, J=7.4, 8.0 Hz, 1H, 6-Hquinoline), 7.21–7.15
(m, 2H, 5-/8-Htetrahydronaphthoyl), 7.15–7.06 (m, 2H, 6-/7Htetrahydronaphthoyl),
5.14 (t, J=6.4 Hz, 1H, 1-Htetrahydronaphthoyl), 2.89–2.74 (m, 2H, 4-
°
at 4 C for 15 min. The formed precipitate was filtered off and
washed with H2O and Et2O. The remaining solid was dried in vacuo,
the product was obtained as a colourless solid (143 mg, 481 μmol,
84%). M.p.=132.5 C. TLC: Rf =0.43 (DCM/MeOH=20/1). 1H-NMR
°
(600 MHz, DMSO-d6, 299 K): δ (in ppm)=7.47 (s, 2H, À NH2), 7.17–
7.11 (m, 2H, 8-Htetrahydronaphthoyl, 6-/7-Htetrahydronaphthoyl), 7.08 (dd, J=8.6,
6.8 Hz, 1H, 6-/7-Htetrahydronaphthoyl), 7.03 (d, J=8.4 Hz, 1H, 5-
Htetrahydronaphthoyl), 2.28–2.20 (m, 1H, 2a-Htetrahydronaphthoyl), 2.18–2.10 (m,
1H, 2b-Htetrahydronaphthoyl), 1.99–1.87 (m, 1H, 3a-Htetrahydronaphthoyl), 1.86–
1.75 (m, 1H, 3b-Htetrahydronaphthoyl). 13C-NMR (151 MHz, DMSO-d6, 299 K):
δ (in ppm)=175.8 (1 C, C=O), 159.7 (1 C, 3-Ctriazolyl), 157.4 (1 C, 3-
H
tetrahydronaphthoyl), 4.90 (t, J=6.4 Hz, 1H, 1-Htetrahdronaphthoyl), 2.84–2.69 (m,
ChemMedChem 2021, 16, 1–20
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