Int. J. Mol. Sci. 2021, 22, 2285
16 of 25
4-((6-Amino-4-(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-3-fluoro-benzonitrile
PPY13): yield: 77%; TLC (EA/PE, 1:1): Rf = 0.38; LC-MS: tR = 9.7 min, >98%; 1H-
(
NMR (400 MHz, CDCl3):
7.39 (dd, J = 7.9, 2.6 Hz, 1H), 7.25-7.11 (m, 2H), 6.66 (dd, J 3.6, 1.7 Hz, 1H), 5.67 (s, 2H),
5.38 (s, NH2); 19F-NMR (377 MHz, CDCl3): 111.64; 13C-NMR (101 MHz, CDCl3):
= 161.59 (d, J = 250.6 Hz), 161.11, 156.54, 146.73, 146.71, 136.40 (d, J = 3.1 Hz), 135.85,
δ = 8.32 (s, 1H), 7.76 (d, J = 1.7 Hz, 1H), 7.69-7.49 (m, 1H),
δ
=
−
δ
131.82, 130.89 (d, J = 8.3 Hz), 120.92 (d, J = 21.4 Hz), 119.85 (d, J = 24.9 Hz), 116.15 (d,
J = 2.8 Hz), 115.65, 113.79, 113.21 (d, J = 9.2 Hz), 113.01, 103.84, 77.48, 77.16, 76.84, 47.48;
HRFT-MS (ESI+): m/z = 335.1047 (calcd. 335.1057 for [M+H]+).
3-((6-Amino-4-(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-5-fluoro-benzonitrile
(
PPY14): yield: 85%; TLC (EA/PE, 1:1): Rf = 0.38; LC-MS: tR = 9.7 min, >99%; 1H-NMR
(500 MHz, CDCl3):
J = 1.5 Hz, 1H), 7.26-7.23 (m, 1H), 6.65 (dd, J = 1.8, 3.6 Hz, 1H), 5.48 (s, 1H), 5.32 (s, NH2);
19F-NMR (282 MHz, CDCl3): 109.05 (t, J = 8.4 Hz); 13C-NMR (101 MHz, CDCl3):
δ = 8.31 (s, 1H), 7.75 (s, 1H), 7.49 (s, 1H), 7.39 (t, J = 1.4 Hz, 1H), 7.28 (d,
δ
=
−
δ = 162.46 (d, J = 251.3 Hz), 161.51, 156.42, 146.55, 141.19 (d, J = 6.5 Hz), 139.68, 135.69,
127.49 (d, J = 3.3 Hz), 125.68 (d, J = 21.9 Hz), 118.65 (d, J = 24.7 Hz), 117.43 (d, J = 3.1 Hz),
115.31, 114.32 (d, J = 9.8 Hz), 112.91, 103.99, 77.48, 48.91; HRFT-MS (ESI+): m/z = 335.1049
(calcd. 335.1057 for [M+H]+).
2-((6-Amino-4-(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-3-fluoro-benzonitrile
(
(
PPY15): yield: 59%; TLC (EA/PE, 1:1): Rf = 0.38; LC-MS: tR = 9.4 min, >99%; 1H-NMR
300 MHz, CDCl3):
δ
= 8.24 (s, 1H), 7.72 (d, J = 1.7 Hz, 1H), 7.58-7.27 (m, 4H), 6.63 (dd,
112.33
= 161.40 (d, J = 252.4 Hz), 161.24,
J = 3.6, 1.8 Hz, 1H), 5.68 (s, 2H), 5.41 (s, NH2); 19F-NMR (282 MHz, CDCl3):
δ
=
−
(dd, J = 9.3, 5.1 Hz); 13C-NMR (75 MHz, CDCl3):
δ
156.56, 151.72, 150.78, 146.36, 135.45, 130.81 (d, J = 9.0 Hz), 129.41 (d, J = 3.7 Hz), 126.82
(d, J = 17.5 Hz), 120.79 (d, J = 22.0 Hz), 116.43 (d, J = 4.0 Hz), 115.54 (d, J = 5.4 Hz), 114.98,
112.80, 103.82, 42.43; HRFT-MS (ESI+): m/z = 335.1049 (calcd. 335.1057 for [M+H]+).
1-(3-(2-Fluoroethyl)benzyl)-4-(furan-2-yl)-1H-yrazolo[3,4-d]pyrimidin-6-amine (PPY16):
1
yield: 51%; LC-MS: tR = 10.0 min, >99%; H-NMR (400 MHz, CDCl3):
δ = 8.27 (s, 1H),
7.77-7.65 (m, 1H), 7.43 (d, J = 3.5 Hz, 2H), 7.34-7.11 (m, 4H), 6.63 (dd, J = 3.5, 1.7 Hz, 1H),
5.46 (s, 2H), 5.33 (s, NH2), 4.59 (dt, J = 47.1, 6.6 Hz, 2H), 2.97 (dt, J = 23.0, 6.6 Hz, 2H);
19F-NMR (282 MHz, CDCl3):
137.69 (d, J = 6.3 Hz), 137.06, 134.99, 129.82 (d, J = 8.1 Hz), 129.46, 129.04, 128.75, 128.58,
127.60 (d, J = 13.3 Hz), 126.37, 115.83, 112.84, 104.01, 84.07 (d, J = 169.0 Hz), 50.14, 36.93 (d,
J = 20.4 Hz) HRFT-MS (ESI+): m/z = 338.1412 (calcd. 338.1417 for [M+H]+).
δ
=
−
114.63; 13C-NMR (75 MHz, CDCl3):
δ = 146.42, 145.93,
1-(3-(2-Fluoroethoxy)benzyl)-4-(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine (PPY17):
1
yield: 54%; LC-MS: tR = 9.8 min, >99%; H-NMR (400 MHz, CDCl3):
δ = 8.27 (s, 1H),
7.73 (dd, J = 1.7, 0.8 Hz, 1H), 7.48 (s, 1H), 7.23 (t, J = 7.9 Hz, 1H), 6.97-6.78 (m, 3H), 6.64
(dd, J = 3.6, 1.8 Hz, 1H), 5.64-5.14 (m, 4H), 4.84-4.57 (m, 2H), 4.27-4.05 (m, 2H); 19F-NMR
(
377 MHz, CDCl3):
δ
=
−
223.92; 13C-NMR (101 MHz, CDCl3):
δ = 161.27, 158.78, 156.17,
151.79, 150.85, 146.36, 138.48, 134.96, 129.94, 120.82, 115.01, 114.30, 113.99, 112.81, 104.03,
81.98 (d, J = 170.8 Hz), 67.17 (d, J = 20.6 Hz), 50.08; HRFT-MS (ESI+): m/z = 354.1316 (calcd.
354.1366 for [M+H]+).
1-(3-(3-Fluoropropoxy)benzyl)-4-(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine
(
PPY18): yield: 61%; LC-MS: tR = 11.0 min, >95%; 1H-NMR (400 MHz, CDCl3): δ = 8.36
(s, 1H), 7.81-7.74 (m, 1H), 7.46 (d, J = 8.8 Hz, 1H), 7.38 (dd, J = 8.6, 5.4 Hz, 2H), 6.98 (t,
J = 8.7 Hz, 1H), 6.70 (d, J = 3.0 Hz, 1H), 6.37 (d, J = 3.0 Hz, 1H), 5.53 (s, 2H), 4.65-4.46 (m,
4H), 3.93 (t, J = 6.1 Hz, 2H), 2.06 (dt, J = 26.1, 5.9 Hz, 2H); 19F-NMR (377 MHz, CDCl3):
δ = −114.61
; δ = 163.75, 161.30, 159.14, 156.07, 151.66, 146.43,
13C-NMR (101 MHz, CDCl3):
135.03, 132.57 (d, J = 3.1 Hz), 129.83 (d, J = 8.2 Hz), 120.41, 115.69 (d, J = 21.6 Hz), 115.09,
114.03 (d, J = 33.8 Hz), 112.84, 104.03, 80.86 (d, J = 164.4 Hz), 63.57 (d, J = 5.1 Hz), 49.52,
30.12 (d, J = 57.4 Hz); LRFT-MS (ESI+): m/z = 406.29 (calcd. 406.11 for [M+K]+).
1-(2-Fluorophenethyl)-4-(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine (PPY19):
yield: 45%; TLC (EA/PE, 1:1): Rf = 0.46; LC-MS: tR = 10.1 min, >99%; 1H-NMR (400 MHz,
CDCl3):
δ = 8.24 (s, 1H), 7.73 (dd, J = 0.8, 1.7 Hz, 1H), 7.54 (s, 1H), 7.20-7.13 (m, 1H), 7.10-6.87