NJC
Paper
4
-(4-Chlorophenyl)-2-(N,N-dimethylamino)-8-methyl-3,4-dihydro- TLC (silica gel, MeOH : DCM, 1 : 9): R
f
0.51; MS (ESI) m/z 344.1
+
pyrimido[1,2-a][1,3,5]triazin-6-one (5an). Mp 289–290 1C (AcOEt: (MH ); anal. calcd C, 59.47; H, 5.28; N, 20.40; found C, 59.45; H,
EtOH); TLC (silica gel, MeOH : CH Cl , 1 : 6): R 0.52; MS (ESI) m/z 5.26; N, 20.15. H NMR (300 MHz, Me SO-d ): d 2.08 (3H, s,
17.9 (MH ); anal. calcd C, 56.69; H, 5.08; N, 22.04; found C, 8-Me), 3.49–3.70 (8H, m, morpholino), 5.79 (1H, s, H-7), 6.86
6.46; H, 5.19; N, 21.86. H NMR (300 MHz, Me SO-d ): d 2.07 (1H, s, H-4), 7.15–7.30 (4H, m, H-2 , H-3 ,H-5 and H-6 ), 8.90
1
2
2
f
2
6
+
3
5
(
1
0
0
0
0
2
6
1
3
3H, s, Me), 3.02 (6H, s, N(Me)
2
), 5.75 (1H, s, H-7), 6.82 (1H, s, (1H, s, NH). C NMR (75 MHz, Me
2
00
SO-d
6
): 23.7 (Me), 44.5
3
0
0
3
00
00
00
H-4), 7.18 (2H, d, J = 8.7 Hz, H-2 and H-6 ), 7.44 (2H, d, J = (C-3 and C-5 ), 59.2 (C-4), 65.6 (C-2 and C-6 ), 102.7 (C-7),
.7 Hz, H-3 and H-5 ), 8.74 (1H, s, NH). C NMR (75 MHz, 115.5 (d, JC–F = 21.8 Hz, C-3 and C-5 ), 127.4 (d, JC–F = 8.8 Hz,
2 6 2
Me SO-d ): d 23.6 (Me), 36.6 (N(Me) ), 59.3 (C-4), 102.1 (C-7), C-2 and C-6 ), 135.6 (d, JC–F = 2.4 Hz, C-1 ), 153.4 (C-2), 155.0
0
0
13
2
0
0
3
8
0
0
4
0
0
0
0
0
0
1
0
1
(
27.1 (C-2 and C-6 ), 128.7 (C-3 and C-5 ), 133.1 (C-4 ), 138.5 (C-9a), 160.3 (C-6), 161.9 (d,
JC–F = 245.2, C-4 ), 165.9 (C-8).
0
C-1 ), 153.3 (C-2), 155.5 (C-9a), 160.3 (C-6), 165.7 (C-8). HPLC: HPLC: purity 94.7%, t 16.1 min (MeOH:H O).
R
2
purity 100%, t 19.0 min (MeOH:H O); purity 100%, t 12.8 min
8-Methyl-2-morpholino-(4-trifluoromethylphenyl)-3,4-dihydro-
R
2
R
(
CH CN:H O).
pyrimido[1,2-a][1,3,5]triazin-6-one (5au). Mp 233–234 1C (AcOEt);
3
2
8
-Methyl-2-morpholino-4-phenyl-3,4-dihydropyrimido[1,2-a]- TLC (silica gel, MeOH: DCM, 1: 9): R
f
0.52; MS (ESI) m/z 394.1
+
[
1,3,5]triazin-6-one (5aq). Mp 272–273 1C (EtOH); TLC (silica gel, (MH ); anal. calcd C, 54.96; H, 4.61; N, 17.80; found C, 54.80; H,
MeOH : CH Cl , 1 : 9): R 0.48; MS (ESI) m/z 326.1 (MH ); anal. 4.58; N, 17.73. H NMR (300 MHz, Me SO-d ): d 2.10 (1H, s, Me)
2 2 f 2 6
+
1
calcd C, 62.75; H, 5.89; N, 21.52; found C, 62.51; H, 5.80; N, 3.48–3.71 (8H, m morpholino), 5.83 (1H, s, H-7), 6.94, (1H, s,
1
3
0
0
3
2
(
(
1.35. H NMR (300 MHz, Me
2 6
SO-d ): 2.08 (3H, s, Me), 3.36–3.71 H-4), 7.41 (2H, d, J = 7.9 Hz, H-2 and H-6 ), 7.77 (2H, d, J =
0
0
13
8H, m, morpholino), 5.79 (1H, s, H-7), 6.87 (1H, br s, H-4), 7.18 7.9 Hz, H-3 and H-5 ), 9.02 (1H, br s, NH). C NMR (75 MHz,
2H, d, J = 7.5 Hz, H-2 and H-6 ), 7.30–7.40 (3H, m, H-3 , H-4
and H-5 ), 8.91 (1H, br s, NH); C NMR (75 MHz, Me SO-d ): 102.8 (C-7), 123.9 (q, J
3.8 (8-Me), 44.5 (C-2 and C-6 ), 59.6 (C-4), 65.6 (C-3 and C-5 ), 3.5 Hz, C-3 and C-5 ), 126.2 (C-2 and C-6 ), 129.1 (q,
02.6 (C-7), 125.1 (C-2 and C-6 ), 128.5 (C-4 ), 128.6 (C-3 and 31.8 Hz, C-4 ), 143.9 (C-1 ), 153.5 (C-2), 154.8 (C-9a), 160.3 (C-6),
C-5 ), 139.3 (C-1 ), 153.5 (C-2), 155.1 (C-9a), 160.4 (C-6), 165.8 165.9 (C-8). HPLC: purity 100%, t
0
0
0
0
00 00 00 00
Me SO-d ): 44.7 (C-3 and C-5 ), 60.1 (C-4), 65.6 (C-2 and C-6 ),
2 6
0
13
1
3
= 272.1 Hz, p-CF ), 125.8 (q, J
C–F
=
=
2
6
00
C–F
3
0
00
00
00
0
0
0
0
2
2
1
J
C–F
0
0
0
0
0
0
0
R 2
20.3 min (MeOH:H O).
(C-8); IR (KBr); n 3390 br NH, 2980 (CH), 1670 CQO, 1616, 4-(8-Methyl-2-morpholino-6-oxo-4,6-dihydro-3H-pyrimido-
1481, 1388, 1296, 1203, 966. HPLC: purity 98.4%, t
R
15.2 min [1,2-a][1,3,5]triazin-4-yl)benzonitrile (5av). Mp 269–270 1C
(
MeOH:H O).
(MeOH); TLC (silica gel, AcOEt : hexane, 8 : 2): R 0.18; MS
2
f
+
2-Morpholino-4-(methylphenyl)-8-methyl-3,4-dihydropyrimido- (ESI) m/z 351.1 (MH ); anal. calcd C, 61.70; H, 5.18; N, 23.99;
1
[1,2-a][1,3,5]triazin-6-one (5ar). Mp 211–212 1C (AcOEt:EtOH); TLC found C, 61.60; H, 5.13; N, 23.72. H NMR (300 MHz, Me SO-
2
+
(silica gel, MeOH : DCM, 1 : 9): R
f
0.49; MS (ESI) m/z 340.1 (MH );
d
6
): d 2.09 (3H, s, Me), 3.48–3.69 (8H, m, morpholino), 5.82
3
0
anal. calcd C, 63.70; H, 6.24; N, 20.64; found C, 61.88; H, 6.05; N, (1H, s, H-7), 6.92 (1H, s, H-4), 7.35 (2H, d, J = 8.3 Hz, H-2 and
1
1
0
3
0
0
9.87. H NMR (300 MHz, Me
2
SO-d
6
): d 2.07 (3H, s, 8-Me), 2.26 H-6 ), 7.86 (2H, d, J = 8.3 Hz, H-3 and H-5 ), 8.99 (1H, s, NH).
0
13
00
00
(3H, s, 4 -Me) 3.48–3.69 (8H, m, morpholino), 5.78 (1H, s, H-7),
C NMR (75 MHz, Me
2
SO-d
6
): 23.7 (Me), 44.7 (C-3 and C-5 ),
3
0
0
00
00
0
6
.83 (1H, s, H-4), 7.06 (2H, d, J = 7.9 Hz, H-2 and H-6 ), 7.16 (2H, 59.5 (C-4), 65.6 (C-2 and C-6 ), 102.7 (C-7), 111.4 (C-4 ), 118.3
3
0
0
13
0
0
0
0
0
d, J = 7.9 Hz, H-3 and H-5 ), 8.94 (1H, br s, NH). C NMR (CN), 126.3 (C-2 and C-6 ), 132.8 (C-3 and C-5 ), 144.5 (C-1 ),
0 00
75 MHz, Me SO-d ): 20.5 (4 -Me), 23.7 (8-Me), 44.5 (C-3 and 153.3 (C-2), 154.9 (C-9a), 160.3 (C-6), 166.1 (C-8). HPLC: purity
2 6
(
0
0
00
0
00
0
C-5 ), 59.7 (C-4), 65.6 (C-2 and C-6 ), 102.6 (C-7), 125.1 (C-2 and 100%, tR 19.1 min (MeOH:H O).
2
0
0
0
0
C-6 ), 129.1 (C-3 and C-5 ), 136.5 (C-1 ), 137.8 (C-4 ), 153.5 (C-2),
55.0 (C-9a), 160.4 (C-6), 165.4 (C-8); IR (KBr); n 3398 br NH, 2988 [1,2-a][1,3,5]triazin-6-one (5ax). Mp 267–268 1C (decomposed)
CH), 1672 CQO, 1620, 1418, 1308, 1211, 967. HPLC: purity (EtOH); TLC (silica gel, MeOH : DCM, 1 : 9): R 0.41; MS (ESI) m/z
332.1 (MH ); anal. calcd C, 54.36; H, 5.17; N, 21.13, S, 9.68; found
8-Methyl-2-morpholino-4-(thiophen-2-yl)-3,4-dihydropyrimido-
1
(
f
+
9
9.6%, t
-(4-Methoxyphenyl)-8-methyl-2-morpholino-3,4-dihydropyrimido- C, 54.23; H, 5.05; N, 21.09, S, 9.60. H NMR (300 MHz, Me
1,2-a][1,3,5]triazin-6-one (5as). Mp 203–204 1C (Ether); TLC d 2.05 (3H, s, Me), 3.49–3.78 (8H, m, morpholino), 5.79 (1H, s,
R 2
17.6 min (MeOH:H O).
1
4
2 6
SO-d ):
[
(
(
0
0
silica gel, MeOH : DCM, 1 : 9): R 0.53; MS (ESI) m/z 356.1 H-7), 6.89–7.00 (2H, m, H-4, H-4 ), 7.06 (1H, m, H-3 ), 7.45 (1H,
f
+
0
13
MH ); anal. calcd C, 60.83; H, 5.96; N, 19.71; found C, 60.26; dd, J = 4.9 Hz, J = 1.1 Hz, H-5 ), 8.97 (1H, s, NH). C NMR
1
00
00
H, 5.86; N, 19.39. H NMR (300 MHz, Me
Me), 3.46–3.67 (8H, m, morpholino), 3.72 (3H, s, OMe), 5.78 65.7 (C-2 and C-6 ), 102.8 (C-7), 125.1, 126.3, 126.7, 142.8 (C-2 ),
2
SO-d
6
): d 2.07 (3H, s, (75 MHz, Me
2
SO-d
6
00
): 23.6 (Me), 44.6 (C-3 and C-5 ), 56.9 (C-4),
00
0
3
0
(1H, s, H-7), 6.83 (1H, s, H-4), 6.91 (2H, d, J = 8.7 Hz, H-3 and 152.7 (C-2), 154.9 (C-9a), 160.0 (C-6), 165.8 (C-8); IR (KBr); n 3400
0
3
0
0
H-5 ), 7.12 (2H, d, J = 8.7 Hz, H-2 and H-6 ), 8.89 (1H, s, NH). br NH, 3097, 2991 (CH), 1674 CQO, 1620, 1530, 1477, 881, 760.
1
3
00
00
C NMR (75 MHz, Me
2
SO-d
6
): 23.7 (Me) 44.7 (C-3 and C-5 ), HPLC: purity 99.4%, t
R
14.1 min (MeOH:H
4-(4-Bromophenyl)-8-methyl-2-morpholino-3,4-dihydro-pyrimido-
C-3 and 5 ), 126.5 (C-2 and C-6 ), 131.4 (C-1 ), 153.5 (C-2), [1,2-a][1,3,5]triazin-6-one (5az). Mp 245–246 1C (MeOH); TLC (silica
2
O).
0
0
00
5
(
5.1 (OMe), 59.4 (C-4), 65.7 (C-2 and C-6 ), 102.7 (C-7), 113.9
0
0
0
0
0
0
55.1 (C-9a), 159.3 (C-4 ), 160.4 (C-6), 165.7 (C-8). HPLC: purity gel, MeOH : DCM, 1 : 9): R 0.60; MS (ESI) m/z 404.1, 406.1 (MH );
f
+
1
1
00%, t
-(4-Fluorophenyl)-8-methyl-2-morpholin-4-yl-3,4-dihydro- N, 17.32. H NMR (300 MHz, Me
pyrimido[1,2-a][1,3,5]triazin-6-one (5at). Mp 269–270 1C (EtOH); 3.60 (8H, s, morpholino), 5.80 (1H,s, H-7), 6.83 (1H, s, H-4),
R
15.3 min (MeOH:H
2
O).
anal. calcd C, 50.51; H, 4.49; N, 17.32; found C, 50.50; H, 4.27;
1
4
2 6
SO-d ): d 2.08 (3H, s, Me),
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New J. Chem.