Metalation of Biginelli compounds. A general unprecedented route to C-6 functionalized 4-aryl-3,4-dihydropyrimidinones

Article abstract of DOI:10.1021/jo050675q

4-Aryl-6-methyl-3,4-dihydro-2(1H)-pyrimidinone esters (DHPMs) readily undergo metalation at the C-6 methyl (vinylogous ester) position on treatment with lithium diisopropylamide at -10 °C. The resulting anion intermediates can be treated with electrophili

Full text of DOI:10.1021/jo050675q

TABLE 1. Deuterium Incorporation and Condition
Optimization for Metalation of Dihydropyrimidinone 1a
Metalation of Biginelli Compounds. A
General Unprecedented Route to C-6
Functionalized
4-Aryl-3,4-dihydropyrimidinones
Kamaljit Singh,* Sukhdeep Singh, and Aman Mahajan
Department of Applied Chemical Sciences & Technology,
Guru Nanak Dev University, Amritsar - 143 005, India
Kamaljit19in@yahoo.co.in
Received April 6, 2005
electrophile
(temp)
base
isolated
entry
(equiv)
product yield (%)
1
2
3
4
5
6
7
d4-methanol (r.t.) LDA (3.1)
3a
3b
3b
3b
3b
3b
3b
70
55
50
55
56
60
71
EtBr (0 °C)
EtBr (0 °C)
EtBr (0 °C)
EtBr (0 °C)
EtBr (0 °C)
EtBr (0 °C)
n-BuLi (2.1)
n-BuLi (3.1)
n-BuLi (4.1)
n-BuLi (5.1)
LDA (3.1)
LDA (4.1)
ridines (NADH analogues),4 the elaborated DHPMs are
considered to be conformationally flexible, and the con-
sequent effects on the calcium channel modulatory activi-
ties are well-documented.5 To the best of our knowledge,
the only report for the functionalization of the C-6 methyl
group is through bromination (invariably plagued by
gem-dibromination) and subsequent reaction with some
nucleophiles.2e,f In view of the potential usefulness of the
C-6 elaborated DHPMs,6 we have undertaken this in-
vestigation, and in this note, we report the first rational
synthesis of C-6 elaborated DHPMs.
4-Aryl-6-methyl-3,4-dihydro-2(1H)-pyrimidinone
esters
(DHPMs) readily undergo metalation at the C-6 methyl
(vinylogous ester) position on treatment with lithium diiso-
propylamide at -10 °C. The resulting anion intermediates
can be treated with electrophilic reagents to afford func-
tionalized DHPMs that have been chemically elaborated
mainly at the C-6 position. Di- and trianion formation is also
possible at both the vinylogous methyl and NH positions
when reactions are performed with excess equivalents of the
base.
We initially examined the metalation of the simple
5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydro-2(1H)-
pyrimidinone 1a with LDA (-10 °C) and subsequent
quenching at ambient temperature with d4-methanol to
determine optimal conditions for vinylogous C-6 meth-
ylmetalation. Deuterium distribution (%-d1 incorporation
and location) in the resultant product was determined
A careful examination of the current literature has
revealed that elaboration of C-6 of 4-aryl-6-methyl-3,4-
dihydro-2(1H)-pyrimidinone esters (Biginelli DHPMs)1
through reactions of the lithio salts with electrophiles are
unprecedented. Strategies for the synthesis of the DHPM
nucleus have varied from one-step to multistep approach,
but the methods1,2 for the peripheral elaboration are
scarce2e,f or of limited synthetic scope. The privileged
DHPMs have emerged as the integral backbone of several
calcium channel blockers, antihypertensive agents, R-1a-
antagonists, and marine alkaloids. Most notable among
these are the batzelladine alkaloids, which are found to
be potent HIVgp-120-CD4 inhibitors.3 The scaffold
decoration2h of DHPMs is highly important for creating
structural diversity to produce “druglike” molecules for
biological screening. In analogy with the 1,4-dihydropy-
1
by the high field H and 13C analyses and was found to
be exclusively at the C-6 methyl (vinylogous ester) (100%-
d1) as indicated by the exclusive formation of 3a (entry
1, Table 1). No deuterium incorporation was observed at
any other position in the molecule, which indicates the
exclusive metalation of the least acidic and consequently
the most nucleophilic C-6 position. The other two poten-
tial nitrogen centered metalation/substitution sites if
deuterated were exchanged under the aqueous workup
conditions of the method. Moreover, no addition product
resulting from nucleophilic attack at the ester group of
1a was observed. Use of 1.1 equiv of LDA gave no
deuterium incorporation in the molecule.7
(1) Kappe, C. O. Acc. Chem. Res. 2000, 33, 879 and references
therein.
(2) (a) Kappe, C. O.; Stadler, A. Org. React. 2004, 63, 1. (b) Kappe,
C. O. QSAR Comb. Sci. 2003, 22, 630. (c) Singh, K.; Singh, J.; Deb, P.
K.; Singh, H. Tetrahedron 1999, 55, 12873. (d) Ma, Y.; Qian, C.; Wang,
L.; Yang, M. J. Org. Chem. 2000, 65, 3864. (e) Zigeuner, G.; Hamberger,
H.; Blaschke, H.; Sterk, H. Monatsh. Chem. 1966, 97, 1408. (f) Kappe,
C. O. Liebigs Ann. Chem. 1990, 505. (g) Perez, R.; Beryozkina, T.;
Zbruyev, O. I.; Haas, W.; Kappe, C. O. J. Comb. Chem. 2002, 4, 501.
(h) Dallinger, D.; Kappe, C. O. Pure Appl. Chem. 2005, 77, 155.
(3) (a) Kappe, C. O. Eur. J. Med. Chem. 2000, 35, 1043. (b) Overman,
L. E.; Rabinowitz, M. H.; Renhowe, P. A. J. Am. Chem. Soc. 1995, 117,
2675. (c) Patil, A. D.; Kumar, N. V.; Kokke, W. C.; Bean, M. F.; Freyer,
A. J.; DeBrosse, C.; Mai, S.; Truneh, A.; Faulkner, D. J. J. Org. Chem.
1995, 60, 1182.
Treatment of 1a with 2.1 equiv of freshly prepared
n-BuLi (2.3 N in hexanes) in THF at -10 °C followed by
stirring at room temperature (r.t.) for 3 h yielded the pale
(4) For a review, see: Goldmann, S.; Stoltefuss, J. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 1559.
(5) Fabian, W. M. F.; Semones, M. A.; Kappe, C. O. J. Mol. Struct.
(THEOCHEM) 1998, 432, 219.
(6) Khanetskyy, B.; Dallinger, D.; Kappe, C. O. J. Comb. Chem.
2004, 6, 884.
(7) Use of n-BuLi was found not to yield satisfactory results.
10.1021/jo050675q CCC: $30.25 © 2005 American Chemical Society
Published on Web 06/23/2005
6114
J. Org. Chem. 2005, 70, 6114-6117

TABLE 2. Reactions of 5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydro-2(1H)-pyrimidinone 1 Anions with
Electrophiles: Formation of 3 and 4
electrophile
(temp)
base
product
(3/4)a
isolated
entry
1
(equiv)
R1
R2
Me
R3
R4
yield (%)
MeI (0 °C and r.t.)
LDA (4.1)
LDA (3.1)
LDA (4.1)
LDA (3.1)
LDA (4.1)
LDA (3.1)
LDA (4.1)
LDA (3.1)
LDA (4.1)
LDA (3.1)
LDA (3.1)
3c
3d
3e
H
Me
-
-
-
26
20
30
10
22
30
5
50
55
37
38
35
62
72
58
8
60
35
30
35
60
40
75
Me
Me
Me
H
H
H
3f
3g
3h
H
CH2Ph
Cl
Me
H
H
H
H
H
-
-
-
2
3
PhCH2Cl (r.t.)
4-Me-C6H4SO2Cl (-78 °C)
4
Me2CO (r.t.)
3i
C(OH)Me2
H
H
H
H
H
H
H
H
H
H
-
4a
4b
4c
3j
-
-
-
Me
Me
CH2Ph
-
LDA (4.1)
LDA (4.1)
LDA (4.1)
LDA (3.1)
LDA (4.1)
LDA (3.1)
5
6
MeCOCH2Ph (0 °C)
4-NO2C6H4CHO (-78 °C)
4-NO2C6H4CH(OH)
7
8
2,4-di-(OMe)C6H3CHO (0 °C)
(n-Pr)2S2 (0 °C)
3k
3l
3m
3n
3o
3p
3q
2,4-di(OMe)C6H3CH(OH)
H
H
H
H
H
H
H
H
-
-
-
-
-
-
-
n-PrS
n-(PrS)2
(PhS)2
H
H
Me3Si
H
H
9
10
11
12
Ph2S2 (0 °C)
LDA (3.1)
LDA (4.1)
LDA (4.1)
LDA (4.1)
H
n-EtCOCl (-5 °C)
HCOOEt
n-EtCO
CHO
H
Me3SiCl (0 °C)
a The formation of any ethyl 2-alkoxy/alkylthio-6-methyl-4-aryl-1,4-dihydropyrimidine-5-carboxylate was not detected.13
yellow colored anion 2.8 After 3 h at r.t., ethyl bromide
(3.0 equiv) was added to the metalation solution cooled
at 0 °C, and the reaction was allowed to warm to room
temperature and quenched with saturated aqueous NH4-
Cl to obtain the C-6 alkylated product 3b. Increasing the
amount of the base (Table 1) did not increase the yield
in any significant way unless LDA (4.1 equiv)9 was
employed when the blood red anion of 1a yielded 3b
(entry 7, Table 1, 71% yield), after quenching with ethyl
bromide. Except for the isolation of DHPM 1a (<10%
yield, recycled), no evidence of the formation of N- or
O-alkylated DHPMs was noticed in these reactions.
We subsequently studied the reaction of metalated 1
with different types of electrophiles (Table 2). Use of
rather reactive methyl iodide gave a complex mixture of
all possible products comprising 3c-f, out of which the
C-6 substituted DHPM 3e was obtained in 30% yield.
Benzyl chloride furnished 3g (entry 2) in 50% yield.
p-Toluenesulfonyl chloride furnished the halogenated
derivative 3h (entry 3)10 in 55% yield. Lithiation of 1a
with 3.1 equiv of LDA at low temperature followed by
treatment with acetone gave a mixture (1:1, approxi-
mately) of DHPM 3i (entry 4, 38%) and lactone 4a (35%)
when the reaction was carried out in the usual manner.
Independent treatment of 3i with p-toluenesulfonic acid
in refluxing toluene furnished 4a (80%). However, in the
reaction of the anion of 1b with acetone, employing 3.1
or 4.1 equiv of LDA, exclusive formation of 4b (62%) was
observed. Likewise, the reaction of the lithio salt of 1a
with phenyl acetone furnished the lactone 4c as a
diastereomeric mixture in 72% yield.11
Reactions of aldehydes (entries 6 and 7, Table 2) were
executed using 4.1 equiv of LDA for anion generation,
and the corresponding C-6 elaborated products 3j and
3k were obtained in 58 and 60% yields, respectively, as
diastereomeric mixtures (7:3 ratio, approximately). The
use of di-n-propyldisulfide as electrophile for quenching
the anion of 1a furnished C-6-mercaptopropyl derivative
3l (entry 8, 35%) along with the bis-substituted thioacetal
3m (30%); the latter was presumably formed through the
deprotonation of more acidic proton adjacent to the
(10) Upon solvent-free heating (210 °C), 3h yielded 4-phenyl-4,7-
dihydro-1H-3H-furo[3,4-d]pyrimidine-2,5-dione 5,2g in 80% yield.
(8) Although a number of lithio intermediates can be envisioned,
metalated 1 in this note is depicted as the C-6 and N-localized anion
for simplicity and clarity.
(11) Isolated in 7:3 ratio. The 1H NMR of the crude mixture was
complex. However, in the 1H NMR spectra of the isolated diastereo-
mers, the chemical shifts showed considerable separation (see Sup-
porting Information).
(9) The anion generation time was also reduced from 3 to 1.5 h.
J. Org. Chem, Vol. 70, No. 15, 2005 6115

TABLE 3. C-6 Elaborated DHPMs from the Metalation
red color was quenched in most of the cases, indicating the
consumption of the carbanion. Stirring was continued for ad-
ditional time (Table 2) to complete the reaction, after which a
saturated aqueous solution of NH4Cl was introduced. The
reaction was treated with brine and extracted with ethyl acetate
(3 × 25 mL). The extracts were dried over anhydrous Na2SO4,
and the mixture was concentrated under reduced pressure. The
products were isolated using flash chromatography using silica
gel-G (60-120 mesh) and mixtures of ethyl acetate/hexane as
eluent. For preparing samples for microanalytical analysis,
crystallization was done using a combination of dry DCM and
hexane or methanol and petroleum ether (entries 3-7; Table
2). The characteristic data of the selected compounds are
presented below.
of 1c-f
isolated
yield (%)
entry
DHPM 1
R5
product
1
2
3
4
1c
1d
1e
1f
4-OMe-C6H4
3r
3s
3t
65
78
72
67
3,4,5-tri(OMe)C6H2
H
Et
3u
Entry 7, Table 1. 5-Ethoxycarbonyl-6-propyl-4-phenyl-
3,4-dihydropyrimidin-2(1H)-one (3b): Creamy white solid;
Rf: 0.5 (30% v/v ethyl acetate/hexane); yield 71%; mp 162-165
°C (DCM); IR (KBr): νmax 3245, 1705, 1665 cm-1 1H NMR
;
mercaptopropyl substituent followed by reaction with di-
n-propyldisulfide. However, in the reaction of diphenyl-
disulfide, C-6 di-substituted DHPM 3n (entry 9, 35%) was
formed exclusively.
The hard electrophile n-propionyl chloride furnished
only N-3 substituted product 3o (entry 10, Table 2) in
60% yield. Likewise, reaction of ethyl formate with the
anion of 1a furnishes N-3 formylated product 3p (entry
11), exclusively. The formation of N-3 acylated DHPMs,
otherwise tedious to synthesize,12a is prized for their
special biological effects.12b Trimethylsilyl chloride
quenched the anion of 1a to furnish the C-6 elaborated
DHPM 3q (entry 12, 75%) exclusively.
To further explore the scope of this methodology, we
performed metalation reactions of various C-4 aryl as
well as alkyl substituted Biginelli substrates with LDA
(4.1 equiv), using ethyl bromide as electrophile (0 °C)
using the standardized procedure. The corresponding C-6
elaborated products were obtained in a synthetically
useful manner (Table 3).
In summary, DHPM derivatives readily undergo vi-
nylogous metalation at the C-6 position with alkyllithium
bases. The resulting anion intermediates can be treated
with a variety of electrophilic reagents to afford impor-
tant C-6 elaborated DHPMs in modest to good yields.14
This methodology permits a variety of electrophilic
functionalities to be introduced at the C-6 methyl position
of variously C-4 substituted DHPMs.
(CDCl3): δ 0.95 (t, 3H, J 7.2 Hz), 1.15 (t, 3H, J 6.9 Hz), 1.62 (m,
2H), 2.66 (m, 2H), 4.06 (q, 2H, J 7.0 Hz), 5.37 (d, 1H, J 3 Hz),
6.43 (br, 1H, NH, exchanged with D2O), 7.25 (m, 5H), 8.68 (br,
1H, NH, exchanged with D2O); 13C NMR (CDCl3): δ 13.7, 14.0,
21.6, 26.8, 33.3, 55.3, 59.8, 100.8, 126.4, 127.7, 128.5, 143.8,
150.6, 153.8, 165.3; Anal. Required for C16H20N2O3: C, 66.65;
H, 6.99; N, 9.72; Found: C, 66.88; H, 6.53; N, 9.65; MS: m/z
288 (M+).
Entry 4, Table 2.5-Ethoxycarbonyl-6-(2-hydroxy-2-meth-
yl-propyl)-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (3i):
White solid; Rf: 0.4 (65% ethyl acetate/hexane); yield: 38%; mp
160-162 °C (methanol); IR (KBr): νmax 3480, 3260, 1695, 1635
1
cm-1; H NMR (CDCl3): δ 1.14 (t, 3H, J 7.2 Hz), 1.33 (s, 3H,),
1.35 (s, 3H), 2.72 (s, 1H), 3.08 (ABq, 2H, J 79.8 Hz, J 14.4 Hz),
4.05 (q, 2H, J 7.2 Hz), 5.42 (d, 1H, J 2.7 Hz), 5.51 (br, 1H, NH,
exchanged with D2O), 7.32 (m, 5H), 8.06 (br, 1H, NH, exchanged
with D2O); 13C NMR (CDCl3): δ 14.0, 29.6, 30.1, 41.3, 56.0, 60.1,
71.8, 73.6, 103.0, 126.6, 127.9, 128.7, 143.7, 147.9, 152.4, 165.9,
and 175.8; Anal. Required for C17H22N2O4: C, 64.13; H, 6.97;
N, 8.80; Found: C, 64.12; H, 6.58; N, 8.55; MS: m/z 318 (M+).
Entry 4, Table 2. 7,7-Dimethyl-4-phenyl-3,4,7,8-tetrahy-
dro-1H-pyrano[4,3-d]pyrimidine-2,5-dione (4a): White solid;
Rf: 0.6 (70% ethyl acetate/hexane); yield: 35%; mp 240 °C
(methanol); IR (KBr): νmax 3274, 1710, 1664 cm-1 1H NMR
;
(CDCl3 + DMSO-d6): δ 1.22 (s, 3H), 1.37 (s, 3H), 2.47 (ABq, 2H,
J 64.2 Hz, J 17.7 Hz), 5.29 (d, 1H J 3.6 Hz) 6.96 (br, 1H, NH,
exchanged with D2O), 7.21 (m, 5H), 9.47 (br, 1H, NH, exchanged
with D2O); 13C NMR (CDCl3 + DMSO-d6): δ 25.9, 28.0, 35.6,
53.4, 97.4, 126.0, 127.2, 128.0, 128.1, 143.0, 145.9, 152.0, and
163.5. Anal. Required for C15H16N2O3: C, 66.16; H, 5.92; N,
10.29; Found: C, 65.82; H, 5.90; N, 9.93; MS: m/z 272 (M+).
Entry 5, Table 2. 7-Benzyl-7-methyl-4-phenyl-3,4,7,8-
tetrahydro-1H-pyrano[4,3-d]pyrimidine-2,5-dione (4c, Ma-
jor Diastereomer): White solid; Rf: 0.5 (80% ethyl acetate/
hexane); yield: 60%; mp 232 °C (ethanol); IR (KBr): νmax 3404,
1693, 1674 cm-1; 1H NMR (CDCl3 + DMSO-d6): δ 1.26 (s, 3H),
2.54 (ABq, 2H, J 74.7 Hz, J 17.4 Hz), 2.98 (m, 2H), 5.19 (d, 1H,
J 1.8 Hz), 7.25 (m, 10H), 7.61 (br, 1H, NH, exchanged with D2O),
Experimental Section
Typical Procedure for C-6 Alkylation of 5-Ethoxycarbon-
yl-6-methyl-4-phenyl-3,4-dihydro-2(1H)-pyrimidinone 1a.
To a suspension of DHPM 1a (1.3 g, 5 mmol) in 10 mL of dry
THF under a blanket of dry N2, LDA (4 equiv in 37 mL of dry
THF) was added dropwise through a cannula at -10 °C. After
the addition, the reaction mixture was warmed to room tem-
perature and stirred for an additional 3 h until blood red colored
carbanion was generated. To this carbanion, the appropriate
electrophile (3.0 equiv), dissolved in 10 mL of dry THF, was
added dropwise. Upon addition of the electrophile (Table 2), the
9.52 (br, 1H, NH, exchanged with D2O); 13C NMR (CDCl3
+
DMSO-d6): 23.4, 29.3, 32.2, 45.2, 52.2, 78.2, 95.7, 125.0, 125.3,
125.9, 126.6, 126.8, 129.1, 134.2, 145.6, 150.2, and 162.0; Anal.
Required for C21H20N2O3: C, 72.40; H, 5.79; N, 8.04; Found: C,
72.84; H, 5.28; N, 7.83. MS: m/z 349 (M+).
Entry 6, Table 2. 5-Ethoxycarbonyl-6-[2-hydroxy-2-(4-
nitro-phenyl)ethyl]-4-phenyl-3,4-dihydropyrimidin-2(1H)-
one (3j, Major Diastereomer): Dark yellow crystalline solid;
Rf: 0.4 (70% ethyl acetate/hexane); yield: 58%; mp 202 °C
(ethanol); IR (KBr): νmax 3577, 3371, 3220, 1697, 1685 cm-1; 1H
NMR (CDCl3 + DMSO-d6): δ 1.12 (t, 3H, J 7.07 Hz), 3.17 (ABX
system, 2H, J 13.5 Hz, J 9.2 Hz, J 2.8 Hz), 4.03 (q, 2H, J 7.1
Hz), 5.14 (dd, 1H, J 9.2 Hz, J 2.8 Hz), 5.25 (m, 1H, OH,
exchanged with D2O), 5.35 (d, 1H, J 2.4 Hz), 6.40 (br, 1H, NH,
exchanged with D2O), 7.31 (m, 5H), 7.67 (d, 2H, J 8.5 Hz), 8.17
(d, 2H, J 8.53 Hz), 8.94 (br, 1H, NH, exchanged with D2O); 13C
NMR (CDCl3 + DMSO-d6): δ 13.7, 55.1, 59.8, 72.0, 101.3, 123.1,
126.1, 126.2, 126.4, 127.4, 128.3, 143.8, 146.6, 148.1, 152.0, 152.2,
(12) (a) Atwal, K. S.; Rovnyak, G. C.; O’Reilly, B. C.; Schwartz, J.
J. Org. Chem. 1989, 54, 5898. (b) Atwal, K. S.; Swanson, B. N.; Unger,
S. E.; Floyd, D. M.; Moreland, S.; Hedberg, A.; O’Reilly, B. C. J. Med.
Chem. 1991, 34, 806.
(13) Eynde, J. J. V.; Audiart, N.; Canonne, V.; Michel, S.; Haverbeke,
Y. V.; Kappe, C. O. Heterocycles 1997, 45, 1967.
(14) The structures of all compounds were supported by 300 MHz
1H and 75 MHz 13C NMR and mass spectra. All compounds gave a
single spot on TLC analysis and correct micro analytical data (see
Supporting Information).
6116 J. Org. Chem., Vol. 70, No. 15, 2005

165.7; Anal. Required for C21H21N3O6: C, 61.31; H, 5.14; N,
10.21; Found: C, 62.02; H, 5.51; N, 9.99; MS: m/z 411 (M+).
Entry 8, Table 2. 5-Ethoxycarbonyl-6-propylmercap-
tomethyl 4-phenyl-3,4-dihydropyrimidin-2(1H)-one (3l):
Creamy white solid; Rf: 0.6 (40% ethyl acetate/hexane); yield:
35%; mp 100-103 °C (DCM); IR (KBr): νmax 3220, 1701, 1639
128.6, 144.2, 150.5, 153.5, and 165.9; Anal. Required for
C
17H24N2O3Si: C, 61.41; H, 7.28; N, 8.43; Found: C, 61.12; H,
7.35; N, 8.16; MS: m/z 333 (M+).
Entry 3, Table 3. 5-Ethoxycarbonyl-6-propyl-1,2,3,4-
tetrahydropyrimidin-2(1H)-one (3t): White crystalline solid;
Rf: 0.45 (45% v/v ethyl acetate/hexane); yield 67%; mp 162-
1
cm-1; H NMR (CDCl3): δ 0.93 (t, 3H, J 7.2 Hz), 1.16 (t, 3H, J
1
164 °C (DCM); IR (KBr): νmax 3253, 3126, 1704, 1654 cm-1; H
7.5 Hz), 1.57 (m, 2H), 2.45 (t, 2H, J 7.2 Hz), 3.97 (ABq, 2H, J
43.4 Hz, j 15.4 Hz), 4.07 (q, 2H, J 7.0 Hz), 5.42 (d, 1H, J 2.4
Hz), 5.72 (br, 1H, NH, exchanged with D2O), 7.29 (m, 5H), 7.70
(br, 1H, NH, exchanged with D2O); 13C NMR (CDCl3): δ 13.3,
14.0, 22.6, 30.7, 33.9, 55.9, 60.3, 103.0, 126.5, 128.0, 128.7, 143.3,
145.5, 152.5, and 165.1; Anal. Required for C17H22N2O3S: C,
61.05; H, 6.63; N, 8.38; Found: C, 59.68; H, 6.17; N, 8.12; MS:
m/z 334 (M+).
NMR (CDCl3): δ 0.98 (t, 3H, J 7.5 Hz), 1.25 (t, 3H, J 7.2 Hz),
1.61 (m, 2H), 2.63 (m, 2H), 4.15 (s, 2H), 4.16 (q, 2H, J 7.2 Hz),
5.42 (br, 1H, NH, exchanged with D2O), 7.33 (br, 1H, NH,
exchanged with D2O); 13C NMR (CDCl3): δ 13.7, 14.2, 21.3, 33.4,
59.9, 96.2, 151.0, 154.2, and 165.4; Anal. Required for C10H16
-
N2O3: C, 56.59; H, 7.60; N, 13.20 Found: C, 56.36; H, 8.0; N,
13.60; MS: m/z 212 (M+).
Entry 12, Table 2. 5-Ethoxycarbonyl-6-trimethylsilanyl-
methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (3q): Pale
yellow solid; Rf: 0.5 (30% ethyl acetate/hexane); yield: 75%; mp
Acknowledgment. We thank CSIR (Project 01-
(1960)/04/EMR-II), New Delhi, for financial assistance.
1
185 °C (DCM); IR (KBr): νmax 3238, 1699, 1635 cm-1; H NMR
(CDCl3): δ 0.10 (s, 9H), 1.19 (t, 3H, J 7.2 Hz), 2.49 (ABq, 2H, J
56.1 Hz, J 12.5 Hz), 4.08 (q, 2H, J 7.0 Hz), 5.43 (br, 1H, NH,
exchanged with D2O), 5.44 (d, 1H, J 2.8 Hz), 6.68 (br, 1H, NH,
exchanged with D2O), 7.34 (m, 5H); 13C NMR (CDCl3): δ -1.1,
14.1, 23.6, 55.4, 59.6, 98.4, 126.5, 126.5, 127.6, 127.8, 128.5,
Supporting Information Available: Characterization
data and 1H/13C spectra of all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
JO050675Q
J. Org. Chem, Vol. 70, No. 15, 2005 6117