S. Poudapally, V. Gurram, R. Garlapati, C. Tulluri, U. Addepally,
K. Vidya, S. Sharma, S. Sen, and N. Pottabathini
Vol 000
PdCl2(CH3CN)2 (0.05 eq, 0.0124 mmol) and X-Phos (L3,
0.15 eq, 0.037 mmol), and the mixture was stirred at RT for
cyclopropyl), 1.29 (m, 2H, Ar-H), 1.03 (m, 2H, Ar-H).
13C-NMR (75 MHz, CDCl3): δ 161.9 (amide C=O), 160.0
(Ar-C), 157.8 (Ar-C), 149.1 (Ar-C), 148.4 (Ar-C), 146.9
(Ar-C), 137.1 (Ar-C), 134.6 (Ar-C), 133.5 (Ar-C), 132.1
(Ar-C), 130.2 (Ar-C), 130.0 (Ar-C), 127.0 (Ar-C), 123.8
(Ar-C), 121.7 (Ar-C), 120.5 (Ar-C), 120.0 (Ar-C), 112.0
(Ar-C), 110.6, 92.5, 87.1, 55.8 (Ar-OMe), 44.3 (Ar-Me), 14.4,
9.2 (cyclopropyl). HRMS (ESI): m/z Calcd for C26H22N3O2
[M + H]+ 408.1746; found 408.1712; mp 135–138°C.
2
h. The solvent was filtered and purified by column
chromatography, which was performed using 70% EtOAc in
n-hexane, and dried to obtain pure compound 2b, an off-white
solid: yield 88 mg (90%); Rf (70% EtOAc in n-hexane) = 0.31.
1H-NMR (300 MHz, CDCl3): δ 8.62–8.54 (m, 2H, Ar-H), 8.43
(bs, 1H, Ar-H), 7.83–7.80 (m, 1H, Ar-H), 7.60–7.49 (m, 3H,
Ar-H), 7.28–7.18 (m, 4H, Ar-H), 5.60 (s, 2H, N-CH2), 2.53 (m,
3H, Ar-Me), 1.90–1.88 (m, 1H, cyclopropyl), 1.27–1.26 (m,
2H), 1.02–1.00 (m, 2H). 13C-NMR (75 MHz, CDCl3): δ 161.9
(amide C=O), 157.8 (Ar-C), 149.2 (Ar-C), 148.4 (Ar-C), 146.9
(Ar-C), 140.3 (Ar-C), 137 (Ar-C), 134.6 (Ar-C), 132.1 (Ar-C),
131.9 (Ar-C), 130 (Ar-C), 129.5 (Ar-C), 128.5 (Ar-C), 127.2
(Ar-C), 125.6 (Ar-C), 123.7 (Ar-C), 122.6 (Ar-C), 121.6
(Ar-C), 120.1 (Ar-C), 92.4, 89.6, 44.3 (N-CH2), 20.7 (Ar-Me),
14.4, 9.3 (cyclopropyl). HRMS (ESI): m/z Calcd for
2-Cyclopropyl-6-((3-methoxyphenyl)ethynyl)-3-(pyridin-3-
ylmethyl)quinazolin-4(3H)-one (2e).
This was synthesized
using 6-iodo- and 2-cyclopropyl-3-(pyridin-3-ylmethyl)
quinazolin-4(3H)-one (100 mg, 1 eq, 0.248 mmol), m-anisolyl
acetylene (1 eq, 0.248 mmol), and Et3N (4.5 eq, 1.12 mmol), in
THF (1 mL), and the vial was flushed with argon and added
with PdCl2(CH3CN)2 (0.05 eq, 0.0124 mmol) and X-Phos (L3,
0.15 eq, 0.037 mmol), and the mixture was stirred for RT at
2.5 h. The solvent was filtered and purified by column
chromatography, which was performed using 70% EtOAc in
n-hexane, and dried to obtain pure compound 2e as a white
solid: yield 83 mg (82%); Rf (70% EtOAc in n-hexane) = 0.35.
1H-NMR (300 MHz, CDCl3): δ 8.62–8.50 (m, 2H, Ar-H), 8.44
(m, 1H, Ar-H), 7.83–7.80 (d, J = 8.7 Hz, 1H, Ar-H), 7.60–7.52
(m, 2H, Ar-H), 7.29–7.08 (m, 4H, Ar-H), 6.93 (d, J = 7.8 Hz,
1H, Ar-H), 5.60 (s, 2H, N-CH2), 3.83 (s, 3H, Ar-OMe), 1.89
(m, 1H, cyclopropyl), 1.27 (m, 2H, cyclopropyl), 1.02 (m, 2H,
cyclopropyl). 13C-NMR (75 MHz, CDCl3): δ 161.8 9 (amide
C=O), 159.3 (Ar-C), 157.9 (Ar-C), 149.1 (Ar-C), 148.4 (Ar-C),
147.0 (Ar-C), 137.0 (Ar-C), 134.5 (Ar-C), 132.1 (Ar-C), 130.3
(Ar-C), 129.4 (Ar-C), 127.1 (Ar-C), 124.1 (Ar-C), 123.8
(Ar-C), 123.7 (Ar-C), 121.2 (Ar-C), 120.1 (Ar-C), 116.3
(Ar-C), 115.2 (Ar-C), 90.5, 88.3, 55.2 (N-CH2), 44.3 (Ar-OMe),
14.4, 9.3 (cyclopropyl). HRMS (ESI): m/z Calcd for
C25H19N4O3 [M
+
H]+ 423.1416; found 423.1457; mp
121–123°C.
2-Cyclopropyl-3-(pyridin-3-ylmethyl)-6-(p-tolylethynyl)
quinazolin-4(3H)-one (2c). This was synthesized using
6-iodo- and 2-cyclopropyl-3-(pyridin-3-ylmethyl) quinazolin-
4(3H)-one (100 mg, 1 eq, 0.248 mmol), p-tolyl acetylene (1 eq,
0.248 mmol), and Et3N (4.5 eq, 1.12 mmol), in THF (1 mL),
and the vial was flushed with argon and added with
PdCl2(CH3CN)2 (0.05 eq, 0.0124 mmol) and X-Phos (L3, 0.15
eq, 0.037 mmol), and the mixture was stirred at RT for 2 h. The
solvent was filtered and purified by column chromatography,
which was performed using 70% EtOAc in n-hexane, and dried
to obtain pure compound 2c as a light-yellow solid: yield 68 mg
(70%); Rf (70% EtOAc in n-hexane)
=
0.4. 1H-NMR
(300 MHz, CDCl3): δ 8.61–8.55 (m, 2H, Ar-H), 8.42 (bs, 1H,
Ar-H), 7.82 (dd, J = 8.7 Hz, 1H, Ar-H), 7.60 (m, 2H, Ar-H),
7.45 (d, J = 7.7 Hz, 2H, Ar-H), 7.29–7.26 (m, 1H, Ar-H), 7.17
(d, J = 7.8 Hz, 2H, Ar-H), 5.60 (s, 2H, N-CH2), 2.37 (s, 3H,
Ar-Me), 1.91 (m, 1H, cyclopropyl), 1.25 (m, 2H, cyclopropyl),
1.02 (m, 2H). 13C-NMR (75 MHz, CDCl3): δ 161.9 (amide
C=O), 157.8 (Ar-C), 149.16 (Ar-C), 148.42 (Ar-C), 146.89
(Ar-C), 138.7 (Ar-C), 137.0 (Ar-C), 134.6 (Ar-C), 132.1
(Ar-C), 131.5 (Ar-C), 130.1 (Ar-C), 129.1 (Ar-C), 127.1
(Ar-C), 123.8 (Ar-C), 121.6 (Ar-C), 120.1 (Ar-C), 119.7
(Ar-C), 87.8, 90.9, 44.3 (N-CH2) 21.5 (Ar-Me), 14.4, 9.3
(cyclopropyl). HRMS (ESI): m/z Calcd for C26H22N3O
[M + H]+ 392.1779; found 392.1763; mp 122–125°C.
C26H22N3O2 [M
+
H]+ 408.1759; found 408.1712; mp
155–158°C.
2-Cyclopropyl-6-((4-methoxyphenyl)ethynyl)-3-(pyridin-3-
ylmethyl)quinazolin-4(3H)-one (2f). This was synthesized
using 6-iodo- and 2-cyclopropyl-3-(pyridin-3-ylmethyl)
quinazolin-4(3H)-one (100 mg, 1 eq, 0.248 mmol), p-anisolyl
acetylene (1 eq, 0.248 mmol), and Et3N (4.5 eq, 1.12 mmol), in
THF (1 mL), and the vial was flushed with argon and added
with PdCl2(CH3CN)2 (0.05 eq, 0.0124 mmol) and X-Phos (L3,
0.15 eq, 0.037 mmol), and the mixture was stirred at RT for
2
h. The solvent was filtered and purified by column
2-Cyclopropyl-6-((2-methoxyphenyl)ethynyl)-3-(pyridin-3-
chromatography, which was performed using 70% EtOAc in
n-hexane, and dried to obtain pure compound 2f as an off-white
solid: yield 88 mg (82%); Rf (70% EtOAc in n-hexane) = 0.3.
1H-NMR (400 MHz, CDCl3): δ 8.62 (d, J = 2.5 Hz, 1H, Ar-H),
8.55 (d, J = 4.0 Hz, 1H, Ar-H), 8.40 (d, J = 2.0 Hz, 1H, Ar-H),
7.80–7.77 (dd, J = 8.5, 2.0 Hz, 1H, Ar-H), 7.59 (d, J = 8.0, Hz,
1H, Ar-H, Ar-H), 7.53–7.46 (m, 3H, Ar-H), 7.28–7.25 (m, 1H,
Ar-H), 6.90–6.87 (d, J = 8.8 Hz, 2H, Ar-H), 5.60 (s, 2H,
N-CH2), 3.83 (s, 3H, Ar-OMe), 1.90 (m, 1H), 1.27–1.24 (m,
2H), 1.02 (m, 2H). 13C-NMR (100 MHz, CDCl3): δ 161.9
(amide C=O), 159.8 (Ar-C), 157.7 (Ar-C), 149.1 (Ar-C), 148.4
(Ar-C), 146.8 (Ar-C), 136.9 (Ar-C), 134.5 (Ar-C), 133.1
(Ar-C), 132.1 (Ar-C), 129.9 (Ar-C), 127.1 (Ar-C), 123.7 (Ar-
C), 121.7 (Ar-C), 120.1 (Ar-C), 115.0 (Ar-C), 114.0 (Ar-C),
90.7, 87.3, 55.2 (N-CH2), 44.3 (Ar-OMe), 14.4, 9.2
(cyclopropyl). HRMS (ESI): m/z Calcd for C26H22N3O2
[M + H]+ 408.1661; found 408.1712; mp 138–142°C.
ylmethyl)quinazolin-4(3H)-one (2d).
This was synthesized
using 6-iodo- and 2-cyclopropyl-3-(pyridin-3-ylmethyl)
quinazolin-4(3H)-one (100 mg, 1 eq, 0.248 mmol), o-anisolyl
acetylene (1 eq, 0.248 mmol), and Et3N (4.5 eq, 1.12 mmol), in
THF (1 mL), and the vial was flushed with argon and added
with PdCl2(CH3CN)2 (0.05 eq, 0.0124 mmol) and X-Phos (L3,
0.15 eq, 0.037 mmol), and the mixture was stirred at RT for
2
h. The solvent was filtered and purified by column
chromatography, which was performed using 70% EtOAc in
n-hexane, and dried to obtain pure compound 2d as an
off-white solid: yield 91 mg (82%); Rf (70% EtOAc in
1
n-hexane) = 0.35. H-NMR (300 MHz, CDCl3): δ 8.62 (s, 1H,
Ar-H), 8.56 (d, J = 4.2 Hz, 1H, Ar-H), 8.47 (d, J = 1.5 Hz, 1H,
Ar-H), 7.86 (dd, J = 8.4 Hz, 1H, Ar-H), 7.60–7.50 (m, 3H,
Ar-H), 7.35–7.25 (m, 2H, Ar-H), 6.97–6.90 (m, 2H, Ar-H),
5.60 (s, 2H, N-CH2), 3.93 (s, 3H, Ar-Me), 1.91 (m, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet