Substituted Pyridopyrimidinones, 1: Convenient PTC Alkylation and Halogenation of 2-Hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one 25
2
-[(Oxiran-2-yl)methoxy]-4H-pyrido[1,2-a]pyrimi-
extracted with chloroform. The combined extracts
were dried over anhydrous sodium sulfate, filtered
off and the filtrate was evaporated in vacuum. The
residue was crystallized from the proper solvent to
give the propanolamines 11a,b.
◦
din-4-one (9). mp 150–152 C (ethanol); yield 1.35
g (62%). IR (KBr), νmax(cm ) 1700 (C O), 1633
C N), 1600, 1572, 1527; H NMR (DMSO-d ), δ 3.42
−1
1
(
(
4
7
8
6
m, 1H, CHoxiran), 3.47 (d, J = 5.8 Hz, 2H, CH2oxiran),
.42 (d, J = 5.4 Hz, 2H, OCH
.28 (t, 1H, 7-H), 7.51 (d, 1H, 9-H), 7.96 (t, 1H,
-H), 8.90 (d, 1H, 6-H). Anal Calcd for C11
2
), 5.67 (s, 1H, 3-H),
2-[2-Hydroxy-3-(isopropylamino)propoxy]-4H-py-
◦
H
10
N
2
O
3
rido[1,2-a]pyrimidin-4-one (11a). mp 101–102 C
−
1
(
218.21): C, 60.55; H, 4.62; N, 12.84. Found: C,
(methanol); yield 1.14 g (82%). IR (KBr), νmax(cm )
60.39; H, 4.55; N, 12.82%.
3426 (N H), 1690 (C O), 1624 (C N), 1587, 1512;
1
H NMR (CDCl
3
), δ 1.18 (d, 6H, NCH(CH
3
2
) ), 2.61
(
5-Oxo-5H-oxazolo[3,2-c]pyrido[1,2-a]pyrimidin-11-
(m, 1H, NCH(CH ) ), 2.93 (d, J = 5.6 Hz, 2H,
3
2
◦
ium-1(2H)-ylidene)azanide (14). mp 157–159 C
acetone); yield 1.13 g (56%). IR (KBr), νmax(cm )
707 (C O), 1640 (C N), 1578, 1531; H NMR
NCH CHOH), 3.86 (m, 1H, (CH ) CHOH), 4.11 (d,
2 2 2
−
1
(
1
J = 6.2 Hz, 2H, OCH CHOH), 4.48 (d, 1H, OH), 5.88
2
1
(s, 1H, 3-H), 7.26 (t, 1H, 7-H), 7.49 (d, 1H, 9-H),
(
7
DMSO-d ), δ 4.81 (s, 2H, 2-CH ), 5.83 (s, 1H, 4-H),
.32 (t, 1H, 8-H), 7.82 (d, 1H, 10-H), 7.94 (t, 1H,
6
2
7.71 (t, 1H, 8-H), 9.01 (d, 1H, 6-H). Anal. Calcd for
C H N O (277.33): C, 60.63; H, 5.91; N, 15.15.
1
4
19
3
3
9
-H), 9.08 (d, 1H, 7-H); MS, m/z (I%) 202 (12)
Found: C, 60.45; H, 5.86; N, 14.97%.
+
+
[
M+1] , 201 (100) M , 173 (30), 146 (14), 133 (64),
18 (34), 105 (58), 78 (96), 69 (42). Anal Calcd for
(201.19): C, 59.70; H, 3.51; N, 20.89.
Found: C, 59.60; H, 3.78; N, 20.73%.
1
C
2-[2-Hydroxy-3-(tert-butylamino)propoxy]-4H-py-
◦
10
H
7
N
3
O
2
rido[1,2-a]pyrimidin-4-one (11b). mp 87–89 C
◦
(petroleum ether (60–80 C)); yield 1.08 g (74%). IR
−
1
(
(
KBr), νmax(cm ) 4422 (N H), 1689 (C O), 1618
1
C N), 1578, 1522; H NMR (CDCl
), 2.91 (d, J = 6.0 Hz, 2H, NCH
.88 (m, 1H, (CH
CHOH), 4.18 (d, J = 6.2 Hz, 2H,
OCH CHOH), 4.45 (d, 1H, OH), 5.83 (s, 1H, 3-H),
3
), δ 1.12 (s, 9H,
2
-{2-Hydroxy-3-[(4-oxo-4H-pyrido[1,2-a]
NC(CH
3
3
)
3
2
CHOH),
pyrimidin-2-yl)oxy]propoxy}-4H-pyrido[1,2-
a]pyrimidin-4-one (10)
)
2 2
2
Equimolar amounts (5 mmol) of the oxiran deriva-
tive 9 (1.09 g) and compound 1 (0.81 g) in absolute
ethanol (15 mL) were treated with triethylamine (0.1
7.31 (t, 1H, 7-H), 7.54 (d, 1H, 9-H), 7.76 (t, 1H,
8-H), 8.95 (d, 1H, 6-H). Anal Calcd for C H N O
(291.35): C, 61.84; H, 7.27; N, 14.42. Found: C,
61.60; H, 7.26; N, 14.27%.
1
5
21
3
3
◦
mL), and the mixture was gently warmed at 60 C
for 2 h. The precipitate that formed was then fil-
tered off and crystallized from ethanol (95%) to give
2
-Chloro-4H-pyrido[1,2-a]pyrimidin-4-one (15)
◦
compound 10, mp 218–220 C; yield 1.01 g (53%).
−1
IR (KBr), νmax(cm ) 1700 (C O), 1685 (C O), 1635
A mixture of compound 1 (1.62 g, 10 mmol) and oxa-
lyl chloride (2.7 mL, 30 mmol) was heated on boiling
water bath under reflux for 1 h. Then the reaction
mixture was left to cool and quenched with crushed
ice. The precipitate so formed was then filtered off
and crystallized from water to give the chloroderiva-
tive 15, mp 156–158 C; yield 1.59 g (88%). An au-
thentic sample was prepared using phosphoryl chlo-
ride, mp 156–158 C; yield 0.8 g (44%), according
to lit. [2]. IR (KBr), νmax(cm ) 1709 (C O), 1638
1
(
(
C N), 1570, 1530, 1459; H NMR (DMSO-d
s, 1H, OH), 4.19 (m, 1H, CHOH), 4.35 (d, J = 5.8
CHOH), 5.68 (s, 2H, 3-H), 7.31 (t,
H, 7-H), 7.53 (d, 2H, 9-H), 7.97 (t, 2H, 8-H), 8.92
d, 2H, 6-H). Anal Calcd for C19 (380.36): C,
0.00; H, 4.24; N, 14.73. Found: C, 59.88; H, 4.21;
N, 14.56%.
6
), δ 3.45
Hz, 4H, (OCH
2
(
6
)
2 2
H
16
N
4
O
5
◦
◦
−
1
Addition of Alkyl Amines to Oxirane 9: Preparation
of Propanolamines 11a,b
1
(
C N), 1568, 1524, 1480, 845, 776; H NMR (DMSO-
), δ 6.48 (s, 1H, 3-H), 7.49 (t, 1H, 7-H), 7.72 (d, 1H,
9-H), 8.12 (t, 1H, 8-H), 8.98 (d, 1H, 6-H). Anal Calcd
for C ClN O (180.59): C, 53.21; H, 2.79; Cl, 19.63;
d
6
General Method. A solution of the suitable alkyl
amine (5 mmol), namely iso-propylamine (0.5 mL),
tert-butylamine (0.6 mL) in dioxane (10 mL), was
added to a mixture of oxirane 9 (1.09 g, 5 mmol),
dry potassium carbonate (1.39 g, 10 mmol), and
CTAB (0.5 g) in dioxane (25 mL). Then the mixture
was stirred at room temperature for 24 h. The or-
ganic solution was evaporated to dryness in vacuum,
and the crude residue was treated with water and
8
H
5
2
N, 15.51. Found: C, 53.20; H, 2.66; Cl, 19.50; N,
15.32%.
2,3-Dichloro-4H-pyrido[1,2-a]pyrimidin-4-one (16)
To a mixture of phosphorus pentachloride (5.3 g,
25 mmol) and phosphoryl chloride (4.7 mL,
Heteroatom Chemistry DOI 10.1002/hc