The Journal of Organic Chemistry
Article
Ethyl 4-(Isopropylamino)-6-(1H-pyrazolo[3,4-c]pyridin-1-yl)-
nicotinate (10b). The reaction was carried out on a 500 mg scale
using Procedure A. The product was purified by column
chromatography using EtOAc/n-heptane (2:1) as the eluent to afford
= 8.0, 0.8 Hz, 1H), 8.46 (d, J = 0.8 Hz, 1H), 8.46−8.37 (m, 2H),
7.95−7.92 (dd, J = 8.0, 2 Hz, 1H), 7.86−7.82 (m, 1H), 7.16−7.12 (m,
13
2H), 6.64−6.63 (d, J = 4.0 Hz, 1H). C NMR (100 MHz, DMSO-d ):
6
δ 150.8, 148.2, 147.5, 143.1, 138.2, 129.1, 126.4, 123.3, 120.3, 117.2,
115.7, 102.6. HRMS (ESI-Orbitrap), m/z: [M + H]+ calcd for
C H N , 196.0875; found, 196.0861.
3
02 mg (45%) of compound 10b as an off-white solid (mp 149−151
1
°
C). H NMR (400 MHz, DMSO-d ): δ 10.09 (s, 1H), 8.84 (s, 1H),
6
12
10
3
8
1
2
1
1
2
.60 (d, J = 0.8 Hz, 1H), 8.43 (d, J = 5.2 Hz, 1H), 8.09 (d, J = 7.6 Hz,
H), 7.89 (dd, J = 5.3, 1.3 Hz, 1H), 7.22 (s, 1H), 4.33 (q, J = 7.2 Hz,
H), 3.89 (dd, J = 13.3, 6.8 Hz, 1H), 1.35 (t, J = 7.0 Hz, 3H), 1.32−
1
-(Pyridin-2-yl)-1H-indazole (14c). The reaction was carried out on
a 1.00 g scale using Procedure A. The product was purified by column
chromatography using EtOAc/n-heptane (1:5) as the eluent to afford
.23 (m, 6H). 13C NMR (100 MHz, DMSO-d ): δ 167.4, 156.1, 155.1,
1
6
395 mg (23%) of compound 14c as a white solid (mp 81−83 °C). H
52.9, 141.3, 139.3, 137.9, 135.7, 130.3, 115.7, 105.6, 92.7, 61.1, 43.7,
NMR (400 MHz, DMSO-d ): δ 8.78−8.76 (d, J = 8.8 Hz, 1H), 8.59−
6
2.5, 14.6. HRMS (ESI-Orbitrap), m/z: [M + H]+ calcd for
8
.58 (d, J = 4.8 Hz, 1H), 8.46 (s, 1H), 8.04−8.01 (m, 2H), 7.92−7.90
C H N O , 326.1617; found, 326.1596.
13
1
7
20
5
2
(d, J = 8.0 Hz, 1H), 7.59−7.55 (m, 1H), 7.35−7.31 (m, 2H).
C
Ethyl 4-(Isopropylamino)-6-(1H-pyrazolo[4,3-c]pyridin-1-yl)-
NMR (100 MHz, DMSO-d ): δ 153.6, 147.9, 139.1, 138.1, 137.3,
6
nicotinate (10c). The reaction was carried out on a 250 mg scale
using Procedure A. The product was purified by column
chromatography using EtOAc/n-heptane (2:1) as the eluent to afford
1
28.1, 125.7, 122.6, 121.2, 120.4, 114.8, 112.9. HRMS (ESI-Orbitrap),
m/z: [M + H] calcd for C H N , 196.0875; found, 196.0859.
+
12
10
3
Methyl 1-(Pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
2
88 mg (86%) of compound 10c as an off-white solid (mp 128−130
(
14d). The reaction was carried out on a 500 mg scale using Procedure
1
°
C). H NMR (400 MHz, DMSO-d ): δ 9.22 (d, J = 0.8 Hz, 1H), 8.80
17
6
A. The product was purified by column chromatography using
(
s, 1H), 8.68 (s, 1H), 8.59−8.54 (m, 2H), 8.09 (d, J = 7.6 Hz, 1H),
EtOAc/n-heptane (1:2) as the eluent to afford 952 mg (85%) of
7
1
.23 (s, 1H), 4.35−4.30 (q, J = 7.2 Hz, 2H), 3.91−3.86 (m, 1H),
.37−1.33 (t, J = 7.2 Hz, 3H), 1.29−1.28 (d, J = 6.4 Hz, 6H).
1
compound 14d as a pale brownish solid (mp 134−136 °C). H NMR
13
C
(
400 MHz, CDCl ): δ 9.34 (d, J = 2.0 Hz, 1H), 8.83−8.82 (d, J = 2.4
3
NMR (100 MHz, DMSO-d ): δ 166.8, 155.9, 154.6, 152.2, 145.9,
6
Hz, 1H), 8.72 (m, 1H), 8.40 (m, 2H), 7.96−7.92 (m, 1H), 7.34−7.30
1
45.5, 141.4, 137.8, 122.8, 109.9, 105.0, 92.7, 60.6, 43.1, 21.9, 14.0.
13
(
m, 1H), 4.01 (s, 3H). C NMR (100 MHz, CDCl ): δ 165.7, 151.5,
+
3
HRMS (ESI-Orbitrap), m/z: [M + H] calcd for C H N O ,
17
20
5
2
1
5
2
51.1, 149.0, 139.2, 138.5, 136.3, 132.7, 122.0, 120.9, 117.1, 116.2,
2.5. HRMS (ESI-Orbitrap), m/z: [M + H] calcd for C H N O ,
3
26.1617; found, 326.1590.
Ethyl 4-(Isopropylamino)-6-(1H-pyrazolo[4,3-b]pyridin-1-yl)-
+
1
3
11
4
2
55.0882; found, 255.0863.
-(Pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (14e).
nicotinate (10d). The reaction was carried out on a 250 mg scale
using Procedure A. The product was purified by column
chromatography using EtOAc/n-heptane (2:1) as the eluent to afford
1
The reaction was carried out on a 1.00 g scale using Procedure A.
The product was purified by column chromatography using EtOAc/n-
heptane (2:1) as the eluent to afford 1.79 g (92%) of compound 14e
2
04 mg (61%) of compound 10d as a pale pinkish solid (mp 140−142
1
°C). H NMR (400 MHz, DMSO-d ): δ 9.05−9.03 (d, J = 8.4 Hz,
6
1
as an off-white solid (mp 193−195 °C). H NMR (400 MHz, DMSO-
1
7
6
1
1
9
H), 8.77 (s, 1H), 8.68−8.67 (m, 2H), 8.08−8.06 (d, J = 7.2 Hz, 1H),
.58−7.55 (dd, J = 8.4, 4.4 Hz, 1H), 7.22 (s, 1H), 4.35−4.29 (q, J =
.8 Hz, 2H), 3.91−3.86 (m, 1H), 1.37−1.33 (t, J = 7.2 Hz, 3H), 1.29−
d ): δ 9.06−9.03 (m, 2H), 8.67−8.65 (m, 2H), 8.12−8.10 (m, 2H),
6
7
13
.53−7.50 (m, 1H). C NMR (100 MHz, DMSO-d ): δ 151.7, 150.1,
6
.28 (d, J = 6.4 Hz, 6H). 13C NMR (100 MHz, DMSO-d ): δ 166.8,
149.7, 148.1, 139.0, 136.9, 136.6, 123.1, 117.6, 117.3, 116.1, 103.0.
6
+
HRMS (ESI-Orbitrap), m/z: [M + H] calcd for C H N , 222.0780;
12
8
5
56.0, 154.5, 152.2, 147.1, 143.2, 138.0, 131.9, 123.4, 122.5, 104.9+,
found, 222.0771.
-(Pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (14f).
2.0, 60.5, 43.1, 21.9, 14.0. HRMS (ESI-Orbitrap), m/z: [M + H]
1
calcd for C H N O , 326.1617; found, 326.1603.
17
20
5
2
The reaction was carried out on a 500 mg scale using Procedure A.
The product was purified by column chromatography using EtOAc/n-
heptane (1:4) as the eluent to afford 485 mg (50%) of compound 14f
Ethyl 6-(1H-Indazol-1-yl)-4-(isopropylamino)nicotinate (10e).
The reaction was carried out on a 500 mg scale using Procedure A.
The product was purified by column chromatography using EtOAc/n-
heptane (1:3) as the eluent to afford 268 mg (40%) of compound 10e
1
as an off-white solid (mp 191−193 °C). H NMR (400 MHz, CDCl ):
3
1
δ 8.81−8.79 (d, J = 8.4 Hz, 1H), 8.65 (s, 1H), 8.64−8.51 (m, 2H),
as an off-white solid (mp 91−93 °C). H NMR (400 MHz, DMSO-
8
1
1
.25−8.24 (d, J = 2.0 Hz, 1H), 7.93−7.89 (m, 1H), 7.26−7.23 (m,
d ): δ 8.79−8.76 (m, 2H), 8.47 (s, 1H), 8.03 (d, J = 7.2 Hz, 1H),
6
13
H), 6.74−6.73 (d, J = 4.0 Hz, 1H). C NMR (100 MHz, CDCl ): δ
7
1
1
.90−7.88 (d, J = 8.0 Hz, 1H), 7.57−7.53 (m, 1H), 7.34−7.30 (m,
H), 7.22 (s, 1H), 4.36−4.23 (q, J = 6.8 Hz, 2H), 3.89−3.84 (m, 1H),
3
48.5, 145.8, 141.2, 138.5, 132.7, 129.3, 122.5, 121.5, 118.4, 112.4,
+
13
116.2, 102.9, 102.5. HRMS (ESI-Orbitrap), m/z: [M + H] calcd for
C H N , 221.0827; found, 221.0816.
13
1
was carried out on a 1.00 g scale using Procedure A. The product was
purified by column chromatography using EtOAc/n-heptane (2:1) as
the eluent to afford 1.45 g (84%) of compound 14g as a pale brownish
.37−1.30 (t, J = 7.2 Hz, 3H), 1.30−1.22 (d, J = 6.4 Hz, 6H).
C
NMR (100 MHz, DMSO-d ): δ 166.9, 156.5, 154.4, 152.2, 138.5,
9
4
6
-(Pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine (14g). The reaction
1
1
3
37.9, 128.1, 125.8, 122.7, 121.2, 115.5, 104.6, 92.2, 60.4, 43.0, 21.9,
+
4.0. HRMS (ESI-Orbitrap), m/z: [M + H] calcd for C H N O ,
18
21
4
2
25.1665; found, 325.1638.
-(Pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine (14a). The reaction
1
1
solid (mp 94−96 °C). H NMR (400 MHz, DMSO-d ): δ 9.58 (m,
was carried out on a 1.00 g scale using Procedure A. The product was
purified by column chromatography using EtOAc/n-heptane (3:1) as
the eluent to afford 1.69 g (98.0%) of compound 14a as a brownish
6
1
(
H), 8.75−8.73 (m, 2H), 8.70−8.69 (m, 1H), 8.61 (s, 1H), 8.46−8.43
13
dd, J = 8.0, 1.6 Hz, 1H), 7.48−7.45 (dd, J = 8.0, 4.8 Hz, 1H). C
1
NMR (100 MHz, DMSO-d ): δ 150.2, 149.9, 147.3, 143.1, 142.2,
oil. H NMR (400 MHz, DMSO-d ): δ 8.69−8.64 (dd, J = 4.4, 1.6 Hz,
6
6
1
8
H), 8.64 (s, 1H), 8.49 (s, 1H), 8.39 (dd, J = 8.0, 1.6 Hz, 1H), 8.23−
138.0, 137.2 131.4, 118.9, 117.2. HRMS (ESI-Orbitrap), m/z: [M +
13
+
.21 (m, 1H), 8.09−8.05 (m, 1H), 7.46−7.39 (m, 2H). C NMR
H] calcd for C10
H
8
N
5
, 198.0780; found, 198.0771.
(
100 MHz, DMSO-d ): δ 150.7, 149.9, 149.6, 148.7, 138.7, 135.6,
1-(Pyrimidin-2-yl)-1H-pyrazolo[3,4-b]pyridine (14h). The reaction
was carried out on a 1.00 g scale using Procedure A. The product was
purified by column chromatography using EtOAc/n-heptane (2:1) as
6
1
31.1, 122.2, 118.5, 117.0, 116.7. HRMS (ESI-Orbitrap), m/z: [M +
+
H] calcd for C H N , 197.0827; found, 197.0816.
11
9
4
1
-(Pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine (14b). The reaction was
the eluent to afford 1.69 g (98%) of compound 14h as a brownish
1
carried out on a 1.00 g scale using Procedure A. The product was
purified by column chromatography using EtOAc/n-heptane (1:5) as
the eluent to afford 1.17 g (68%) of compound 14b as a white solid.
The reaction was carried out on a 1.00 g scale using Procedure B.
The product was purified by column chromatography using EtOAc/n-
solid (mp 90−92 °C). H NMR (400 MHz, DMSO-d
6
): δ 9.02 (d, J =
4.8 Hz, 2H), 8.71−8.70 (dd, J = 4.8, 1.6 Hz, 1H), 8.53 (s, 1H), 8.41−
8.39 (dd, J = 8.0, 1.6 Hz, 1H), 7.60−7.58 (t, J = 4.8 Hz, 1H), 7.44−
7.41 (dd, J = 8.0, 4.4 Hz, 1H). 13C NMR (100 MHz, DMSO-d
): δ
6
159.3, 156.3, 150.5, 149.9, 136.6, 130.9, 119.8, 118.9, 117.1. HRMS
(ESI-Orbitrap), m/z: [M + H] calcd for C H N , 198.0780; found,
198.0766.
+
heptane (1:5) as the eluent to afford 1.63 g (95%) of compound 14b
10
8
5
1
(
mp 64−66 °C). H NMR (400 MHz, DMSO-d ): δ 8.48−8.47 (dd, J
6
F
J. Org. Chem. XXXX, XXX, XXX−XXX