M.M.A. Abd El-Mageed et al.
Bioorganic Chemistry 116 (2021) 105336
8.08, 1H, Ar-H), 7.18 (dd, J = 8.12, 1.56, 1H, Ar-H), 7.41–7.45 (m, 2H,
(br s, 4H, 2 CH2 of pyrrolidine), 2.60 (br s, 4H, 2 N(CH2)2 of pyrrolidine),
3.83 (s, 2H, N-CH2), 3.94 (s, 3H, OCH3), 7.11 (s, 1H, Ar-H), 7.34 (s, 1H,
Ar-H), 7.43 (t, J = 7.38, 1H, Ar-H), 7.53 (t, J = 7.58, 2H, Ar-H), 7.62 (s,
1H, CH furan), 7.85 (d, J = 7.32, 2H, Ar-H), 8.13 (s, 1H, CH pyrimidine),
Ar-H), 7.53 (t, J = 7.62, 2H, Ar-H), 7.62 (s, 1H, CH furan), 7.88 (d, J =
–
7.44, 2H, Ar-H), 8.15 (s, 1H, CH pyrimidine), 8.36 (s, 1H, HC N), 9.56
–
(s, 1H, OH, D2O exchangeable), 11.85 (s, 1H, NH, D2O exchangeable).
13
C NMR (DMSO‑d6) δ: 55.68 ( OCH3), 102.29, 102.41, 109.41,
8.36 (s, 1H, HC N), 11.85 (s, 1H, NH, D O exchangeable). 13C NMR
–
–
–
2
116.14, 121.76, 124.84, 126.24, 129.43, 129.49, 129.66, 145.39,
(DMSO‑d6) δ: 23.68 (2 CH2 of pyrrolidine), 53.56 (N(CH2)2 of pyrroli-
–
–
–
–
148.52, 149.11, 151.66, 153.79 (Ar-Cs), 156.36 (HC
N
N), 167.62
dine), 55.77 ( OCH3), 56.44 ( N-CH2), 102.42, 108.14, 121.31,
–
–
–
(
C NH). Anal. Calcd. for C20H16N4O3 (360.37): C, 66.66; H, 4.48; N,
–
124.15, 124.74, 125.23, 129.44, 129.51, 129.65, 145.33, 148.29,
–
–
148.77, 151.61, 153.81 (Ar-Cs), 156.38 (HC N N), 167.63
–
15.55. Found: C, 66.89; H, 4.56; N, 15.78.
–
–
(
C NH). Anal. Calcd. for C25H25N5O3 (443.51): C, 67.70; H, 5.68; N,
–
4.1.7. General procedure for preparation of compounds 12a,b
15.79. Found: C, 67.52; H, 5.85; N, 16.03.
Equimolar amounts of 4-Imino-6-phenylfuro[2,3-d]pyrimidin-3
(4H)-amine 9 and the corresponding 4-(amino substituted) benzalde-
hyde derivative 11a,b (10 mmol) were heated under reflux conditions in
absolute ethanol (10 ml), with or without addition of few drops of
glacial acetic acid, for 4 h. The obtained solid was filtered while hot,
purified from ethanol and dried to give 12a,b, respectively.
4.1.8.2. 4-(((4-Imino-6-phenylfuro[2,3-d]pyrimidin-3(4H)-yl)imino)
methyl)-2-methoxy-6-(piperidin-1-ylmethyl)phenol (14b). Yellowish buff
powder; yield, 53%; m.p., 233–234 ◦C; IR (KBr) νmax./cmꢀ 1: 3417 (OH),
3205 (NH), 3062 (CH aromatic), 2935, 2854, 2800 (CH aliphatic), 1600
(NH bending), 1492 (C C aromatic). 1H NMR (DMSO‑d6 D2O) δ:
–
–
1.45–1.46 (m, 2H, CH2 of piperidine), 1.55–1.57 (m, 4H, 2 CH2 of
piperidine), 2.48–2.51 (m, 4H, N(CH2)2 of piperidine), 3.71 (s, 2H, N-
CH2), 3.94 (s, 3H, OCH3), 7.06 (s, 1H, Ar-H), 7.35 (s, 1H, Ar-H), 7.44 (t,
J = 7.38, 1H, Ar-H), 7.54 (t, J = 7.60, 2H, Ar-H), 7.63 (s, 1H, CH furan),
7.86 (d, J = 7.48, 2H, Ar-H), 8.12 (s, 1H, CH pyrimidine), 8.36 (s, 1H,
4.1.7.1. 3-((4-Morpholinobenzylidene)amino)-6-phenylfuro[2,3-d]pyr-
imidin-4(3H)-imine (12a). Yellow powder; yield, 68%; m.p., > 300 ◦C;
IR (KBr) νmax./cmꢀ 1: 3194 (NH), 3059 (CH aromatic), 2951, 2889, 2858
–
(CH aliphatic), 1604 (NH bending), 1589, 1489, 1438 (C C aromatic).
–
1H NMR (DMSO‑d6 D2O) δ: 3.23 (t, J = 4.48, 4H, N(CH2)2 of morpho-
line), 3.76 (t, J = 4.48, 4H, O(CH2)2 of morpholine), 7.06 (d, J = 8.60,
2H, Ar-H), 7.44 (t, J = 7.32, 1H, Ar-H), 7.54 (t, J = 7.62, 2H, Ar-H), 7.59
HC N), 11.86 (s, 1H, NH, D O exchangeable). 13C NMR (DMSO‑d6) δ:
–
–
2
24.01 (CH2 of piperidine), 25.89 (2 CH2 of piperidine), 53.69 (N(CH2)2
–
–
of piperidine), 55.68 ( OCH3), 60.08 ( N-CH2), 102.10, 102.40,
(s, 1H, CH furan), 7.68 (d, J = 8.56, 2H, Ar-H), 7.93 (d, J = 7.64, 2H, Ar-
108.08, 121.59, 122.95, 124.74, 125.23, 129.44, 129.49, 129.69,
–
–
–
–
H), 8.16 (s, 1H, CH pyrimidine), 8.35 (s, 1H, HC N), 11.78 (s, 1H, NH,
145.40, 148.31, 149.22, 151.66, 153.80 (Ar-Cs), 156.38 (HC N N),
–
D2O exchangeable). 13C NMR (DMSO‑d6) δ: 48.03 (N(CH2)2 of mor-
pholine), 66.44 (O(CH2)2 of morpholine), 102.04, 102.33, 115.14,
125.00, 125.07, 128.51, 129.43, 129.48, 129.62, 145.59, 151.62,
167.58 (
C NH). Anal. Calcd. for C26H27N5O3 (457.53): C, 68.25; H,
–
–
–
5.95; N, 15.31. Found: C, 68.46; H, 6.12; N, 15.53.
–
–
–
–
C
–
–
152.41, 153.78 (Ar-Cs), 156.25 (HC
N
N), 167.59 (
NH). Ms, m/
4.1.8.3. 4-(((4-Imino-6-phenylfuro[2,3-d]pyrimidin-3(4H)-yl)imino)
z (%): 399 (M+, 13.57), 400 (M++1, 13.13). Anal. Calcd. for
C23H21N5O2 (399.45): C, 69.16; H, 5.30; N, 17.53. Found: C, 69.21; H,
5.48; N, 17.40.
methyl)-2-methoxy-6-(morpholinomethyl)phenol (14c). Buff powder;
yield, 73%; m.p., 230–231 C; IR (KBr) νmax./cmꢀ 1: 3410 (OH), 3201
◦
(NH), 3059 (CH aromatic), 2927, 2873, 2827 (CH aliphatic), 1612 (NH
1
–
bending), 1492 (C C aromatic). H NMR (DMSO‑d D2O) δ: 2.48–2.50
–
6
4.1.7.2. 3-((4-(4-Methylpiperazin-1-yl)benzylidene)amino)-6-phenylfuro
[2,3-d]pyrimidin-4(3H)-imine (12b). Yellowish orange powder; yield,
60%; m.p., 280–282 ◦C; IR (KBr) νmax./cmꢀ 1: 3201 (NH), 3059 (CH
(m, 4H, N(CH2)2 of morpholine), 3.61 (t, J = 4.06, 4H, O(CH2)2 of
morpholine), 3.68 (s, 2H, N-CH2), 3.96 (s, 3H, OCH3), 7.15 (s, 1H, Ar-H),
7.36 (s, 1H, Ar-H), 7.44 (t, J = 7.36, 1H, Ar-H), 7.53 (t, J = 7.58, 2H, Ar-
H), 7.63 (s, 1H, CH furan), 7.86 (d, J = 7.36, 2H, Ar-H), 8.14 (s, 1H, CH
aromatic), 2974, 2885, 2835 (CH aliphatic), 1604 (NH bending), 1589,
1
–
–
–
1516, 1489 (C C aromatic). H NMR (DMSO‑d D2O) δ: 2.24 (s, 3H,
pyrimidine), 8.36 (s, 1H, HC N), 11.87 (s, 1H, NH, D O exchangeable).
–
CH3), 2.46 (t, J = 4.66, 4H, N(CH2)2 of N-methylp6iperazine), 3.27 (t, J =
4.62, 4H, N(CH2)2 of N-methylpiperazine), 7.04 (d, J = 8.72, 2H, Ar-H),
7.45 (t, J = 7.32, 1H, Ar-H), 7.55 (t, J = 7.60, 2H, Ar-H), 7.59 (s, 1H, CH
C NMR (DMSO‑d6) δ: 53.25 (N(CH2)2 of morpholine), 55.81 ( OCH3),
2
13
–
– –
N CH2), 66.61 (O(CH2)2 of morpholine), 102.25, 102.42,
58.61 (
108.14, 122.06, 123.17, 124.75, 125.52, 129.46, 129.67, 145.31,
–
–
148.19, 148.31, 151.66, 153.80 (Ar-Cs), 156.35 (HC N N), 167.61
–
furan), 7.65 (d, J = 8.68, 2H, Ar-H), 7.93 (d, J = 7.52, 2H, Ar-H), 8.15 (s,
–
–
–
–
–
1H, CH pyrimidine), 8.34 (s, 1H, HC N), 11.79 (s, 1H, NH, D O
( C NH). Anal. Calcd. for C25H25N5O4 (459.51): C, 65.35; H, 5.48; N,
2
exchangeable). 13C NMR (DMSO‑d6) δ: 46.21 (CH3), 47.66 (N(CH2)2 of
N-methylpiperazine), 54.88 (N(CH2)2 of N-methylpiperazine), 102.02,
102.31, 115.28, 124.59, 124.98, 128.51, 129.41, 129.48, 129.62,
15.24. Found: C, 65.54; H, 5.62; N, 15.56.
4.1.8.4. 4-(((4-Imino-6-phenylfuro[2,3-d]pyrimidin-3(4H)-yl)imino)
methyl)-2-methoxy-6-((4-methylpiperazin-1-yl)methyl)phenol (14d). Yel-
low powder; yield, 67%; m.p., 227–229 ◦C; IR (KBr) νmax./cmꢀ 1: 3425
–
–
–
N N), 167.59
145.64, 151.58, 152.29, 153.78 (Ar-Cs), 156.23 (HC
–
–
(
C NH). Anal. Calcd. for C24H24N6O (412.50): C, 69.88; H, 5.86; N,
–
20.37. Found: C, 69.72; H, 6.02; N, 20.49.
(OH), 3201 (NH), 3055 (CH aromatic), 2943, 2877, 2808 (CH aliphatic),
1
–
1597 (NH bending), 1539, 1492 (C C aromatic). H NMR (DMSO‑d
–
D2O) δ: 2.16 (s, 3H, CH3), 2.35–2.51 (m, 8H, 2 N(CH2)2 of N-methyl6-
piperazine), 3.71 (s, 2H, N-CH2), 3.94 (s, 3H, OCH3), 7.09 (s, 1H, Ar-H),
7.35 (s, 1H, Ar-H), 7.44 (t, J = 7.34, 1H, Ar-H), 7.54 (t, J = 7.62, 2H, Ar-
4.1.8. General procedure for synthesis of compounds 14a-d
4-Hydroxy-3-methoxy-5-(substituted-1-ylmethyl)benzaldehyde de-
rivatives 13a-d (10 mmol) and 4-Imino-6-phenylfuro[2,3-d]pyrimidin-3
(4H)-amine 9 (2.26 g, 10 mmol) with few drops of glacial acetic acid
were refluxed for 4 h in absolute ethanol (10 ml). The obtained solid was
filtered while hot, purified from ethanol and left to dry to give 14a-d,
respectively.
H), 7.63 (s, 1H, CH furan), 7.86 (d, J = 7.48, 2H, Ar-H), 8.13 (s, 1H, CH
–
–
pyrimidine), 8.36 (s, 1H, HC N), 11.87 (s, 1H, NH, D O exchangeable).
2
13C NMR (DMSO‑d6) δ: 46.07 (CH3), 52.57 (N(CH2)2 of N-methyl-
–
piperazine), 55.05 (N(CH2)2 of N-methylpiperazine), 55.76 ( OCH3),
– –
N CH2), 102.43, 108.14, 121.82, 123.11, 124.79, 125.44,
58.84 (
4.1.8.1. 4-(((4-Imino-6-phenylfuro[2,3-d]pyrimidin-3(4H)-yl)imino)
methyl)-2-methoxy-6-(pyrrolidin-1-ylmethyl)phenol (14a). Shiny yellow
powder; yield, 55%; m.p., 210–211 ◦C; IR (KBr) νmax./cmꢀ 1: 3394 (OH),
129.45, 129.50, 129.67, 145.29, 148.32, 148.63, 151.65, 153.82 (Ar-
+
–
–
–
–
–
–
C
Cs), 156.38 (HC
N
N), 167.64 (
NH). Ms, m/z (%): 472 (M ,
12.91). Anal. Calcd. for C26H28N6O3 (472.55): C, 66.09; H, 5.97; N,
17.78. Found: C, 66.23; H, 6.16; N, 17.95.
3197 (NH), 3062 (CH aromatic), 2966 (CH aliphatic), 1597 (NH
1
–
bending), 1554, 1500 (C C aromatic). H NMR (DMSO‑d D2O) δ: 1.77
–
6
16