3,9-Dihydro-2H-[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-ones: First synthesis of the parent heterocycle, 7- and 9-substituted derivatives

Article abstract of DOI:10.1055/s-2000-8721

A first synthesis of 3,9-dihydro-9-aryl-2H-[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-ones is described via the thermal cyclisation of ethyl-(4-aryl-3-oxido-2-quinazolinyl)-carbamates followed by borohydride reduction. A more direct route to 3,9-dihydro-2H-[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-ones, involving the reductive-ring closure of ethyl-(3-oxido-2-quinazolinyl)-carbamate, gives access to the parent unsubstituted heterocycle in good yield. This reaction has been extended to a variety of 7- and 9-substituted 3,9-dihydro-2H-[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-ones.

Full text of DOI:10.1055/s-2000-8721

PAPER
2009
3,9-Dihydro-2H-[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-ones: First Synthesis of
the Parent Heterocycle, 7- and 9-Substituted Derivatives
Patrice P. Renaut,* Philippe Durand, Philippe Ratel
Laboratoires Fournier S.A., 50 rue de Dijon, 21121 Daix, France
Fax +33(3)80447538; E-mail: p.renaut@fournier.fr
Received 30 June 2000
Abstract: A first synthesis of 3,9-dihydro-9-aryl-2H-[1,2,4]-oxadi-
azolo[3,2-b]quinazolin-2-ones is described via the thermal cyclisa-
tion of ethyl-(4-aryl-3-oxido-2-quinazolinyl)-carbamates followed
by borohydride reduction. A more direct route to 3,9-dihydro-2H-
[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-ones, involving the reduc-
tive-ring closure of ethyl-(3-oxido-2-quinazolinyl)-carbamate,
gives access to the parent unsubstituted heterocycle in good yield.
This reaction has been extended to a variety of 7- and 9-substituted
3,9-dihydro-2H-[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-ones.
Keywords: [1,2,4]oxadiazolo[3,2-b]quinazolin-2-one, thermal cy-
clisation, borohydride reduction, reductive-ring closure
Scheme 1
The dihydro derivative 1 may be obtained by reduction
(R2 = H) or by the addition of a nucleophile (R2 = OR or
NR2) on the intermediate 2. By analogy with Katritzky’s
cyclisation of ethyl-(1-oxido-2-pyrimidinyl)-carbamate,1
the intermediate 2 could be obtained from ethyl-(3-oxido-
2-quinazolinyl)-carbamates 3, which were synthesised ac-
cording to Scheme 2.
The 1,2,3,5-tetrahydro-imidazo[2,1-b]quinazolin-2[3H]-
one ring system is a common pharmacophore found in
several phosphodiesterase (PDE) inhibitors such as
Anagrelide (BL-4162A), DH-6471 and Revizinone
(R-80122).
Figure PDE inhibitors based on the 1,2,3,5-tetrahydro-imida-
zo[2,1-b]quinazolin-2[3H]-one ring system
Scheme 2
This route is a modification of the reported synthesis of
ethyl-(4-methyl-3-oxido-2-quinazolinyl)-carbamate 3c.2
Reaction of ethoxycarbonyl isothiocyanate with the
known amino oximes 4a-f in ethyl acetate gave the inter-
mediate thioureas, which spontaneously cyclised in re-
fluxing ethanol to afford the desired substituted ethyl-(3-
oxido-2-quinazolinyl)-carbamates 3a-f in good yields.
Either E, Z or a mixture of E- and Z-oximes can be used
as starting material. In particular, we have shown that
E-oxime 4c and Z-oxime 4c can be separately and effi-
ciently converted to 3c.
Bioisosteric replacement is an efficient way to discover
new biologically active compounds. As part of a program
aimed at the discovery of new PDE inhibitors, we investi-
gated the possible replacement of the CH2 of the imida-
zolinone ring of the PDE pharmacophore by either a NH
or an O. We report here the development of synthetic
routes to the previously unreported 3,9-dihydro-2H-
[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-one ring system 1.
Our first retrosynthetic approach to 3,9-dihydro-2H-
[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-ones was the fol-
lowing :
The thermal cyclisation of the oxides 3 was then investi-
gated (Scheme 3). To be efficient, this reaction required
Synthesis 2000, No. 14, 2009–2012 ISSN 0039-7881 © Thieme Stuttgart · New York

2010
P. P. Renaut et al.
PAPER
drastic conditions: the quinazoline oxides (3a-d) were N-oxides generally leads to the deoxygenated products3
heated at 220 °C under 0.1 Torr for 10-20 minutes. In the instead of the corresponding cyclic hydroxylamines.
case of 4-aryl derivatives, this reaction afforded very However, reduction of nitrones to hydroxylamines is well
clean products 2a,b, whose spectroscopic characteristics documented.4 We anticipated that if the C-4, N-3 double
1
are in agreement with the proposed structures. The H bond is reactive enough towards, for example, sodium
NMR spectra of 2a,b showed the disappearance of the borohydride, the resulting intermediate hydroxylamine
ethyl group and the presence of aromatic protons only. (or probably its corresponding oxy-anion) could attack the
The IR spectra showed a strong n CO band at 1805 cm-1. carbonyl of ethyl carbamate to afford the desired product
However, these products were found to be air sensitive in one step (Scheme 5).
and should be kept under an inert atmosphere or used di-
rectly in the next step. Refluxing compound 2a with alco-
hols, e.g., methanol, afforded the adduct 5 (Scheme 4).
Surprisingly, reaction of 2a with amines such as 1,2,3,6-
tetrahydropyridine in toluene at 100 °C gave the urea 6.
Finally, the reaction of sodium borohydride in a non-nu-
cleophilic solvent such as DMF with 2a and 2b led to the
desired dihydro derivatives 1a and 1b.
Scheme 5
This reaction proceeded smoothly in ethanol and allowed
the synthesis of the desired parent heterocycle 1d. From
3c, we could isolate the intermediate hydroxylamine
which then cyclised to the target product 1c. The general-
ity of this synthesis is exemplified by the synthesis of the
Scheme 3
diversely substituted heterocycles 1c-f. Finally, the N-ox-
ide 3a was directly reduced with a 75% yield to a product
(1a), which proved to be identical in all respects to that
obtained according to Scheme 4. In conclusion, the two
methods described in this paper could give access to a
large variety of compounds encompassing the new 3,9-di-
hydro-2H-[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-one
ring system.
Mps were determined on a Büchi melting point apparatus and are
uncorrected. IR spectra were measured on a Perkin-Elmer 782
1
spectrophotometer. H and 13C NMR spectra were obtained on a
Bruker WP 80 and AC 300 spectrometers using TMS as internal ref-
erence. MS spectra were measured with a Nermag Model R30-10
spectrometer. Structural assignments for all new compounds are
consistent with their spectra. Elemental analyses were performed on
a Perkin-Elmer 240C apparatus.
Ethyl 3-Oxido-4-phenylquinazolin-2-ylcarbamate (3a)
To a solution of 4a5 (10.8 g, 50 mmol) in EtOAc (100 mL) was add-
ed dropwise ethoxycarbonyl isothiocyanate (6.7 g, 51 mmol) over
30 min. The mixture was stirred for 5 h at r.t. and cooled to -18 °C
for 1 h. The resulting precipitate was filtered (15.3 g) and suspended
in absolute EtOH (300 mL). The mixture was refluxed for 6 h and
cooled to -18 °C overnight. The precipitate was filtered and recrys-
tallised from 95% EtOH to afford the desired product 3a (10.4 g,
68%) as a white powder; mp: 180-182 °C.
IR (KBr): n = 3300, 1765, 1620, 1510, 1220, 1170 cm-1.
1H NMR (80 MHz, CDCl3): d = 1.38 (t, 3H, J = 7.6 Hz), 4.36 (q, 2H,
J = 7.6 Hz), 7.20-8.10 (m, 9H), 10.1 (s, 1H).
Scheme 4
In contrast to the 4-aryl derivatives 3a, b, the thermal re-
action conditions applied to 4-methyl (R1 = Me) or to un-
substituted (R1 = H) N-oxides (3c, d) led only to
intractable reaction mixtures. To circumvent this prob-
lem, we investigated a second route to the desired 3,9-di-
hydro-2H-[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-ones
starting from the same N-oxides 3 but involving the attack
of a hydride on the C-4, N-3 double bond in order to trig-
13C NMR (20 MHz, CDCl3): d = 14.1, 62.5, 121.2, 125.7, 126.2,
127.4, 128.0, 128.3, 129.1, 130.2, 130.7, 132.1, 141.4, 145.8, 151.2.
Anal. Calcd for C17H15N3O3 (309.33): C, 66.00; H, 4.89; N, 13.58.
ger the ring closure. Hydride reduction of heteroaromatic Found: C, 65.96; H, 4.86; N, 13.49.
Synthesis 2000, No. 14, 2009–2012 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
3,9-Dihydro-2H-[1,2,4]-oxadiazolo[3,2-b]quinazolin-2-ones
2011
Ethyl 6-Chloro-3-oxido-4-phenylquinazolin-2-ylcarbamate
(3b)
1.3 mmol) to give 3f as a yellowish solid (0.20 g, 58%); mp: 144 °C
(EtOH).
The title compound was prepared as described for 3a, starting from
4b6 (24.0 g, 97.3 mmol) and ethoxycarbonyl isothiocyanate
(14.03 g, 107 mmol) to provide a precipitate which was recrystal-
lised from i-PrOH to give 3b as white crystals (27.42 g, 70%). The
product crystallised with one molecule of i-PrOH; mp: 189 °C.
IR (KBr): n = 3260, 1760, 1620, 1525, 1500, 1380, 1235 cm-1.
1H NMR (80 MHz, DMSO-d6): d = 1.29 (t, 3H, J = 7.1 Hz), 3.88 (s,
3H), 4.24 (q, 2H, J = 7.1 Hz), 7.20-7.50 (m, 2H), 7.70 (d, 1H,
J = 9.4 Hz), 9.26 (s, 1H), 9.90 (s, 1H).
13C NMR (20 MHz, DMSO-d6): d = 14.1, 55.7, 61.6, 103.7, 122.5,
124.3, 127.9, 135.8, 139.3, 143.9, 150.5, 158.0.
IR (KBr): n = 3240, 1765, 1625, 1505, 1230, 1155 cm-1.
1H NMR (80 MHz, Pyridine-d5): d = 1.21 (t, 3H, J = 7.1 Hz), 1.32
(d, 6H, J = 7.5 Hz), 4.05 (sep, 1H, J = 7.5 Hz), 4.31 (q, 2H, J = 7.1
Hz), 7.45 (d, 1H, J = 1.5 Hz), 7.40-7.90 (m, 6H), 8.05 (d, 1H,
J = 6.7 Hz).
Anal. Calcd for C12H13N3O4 (263.26): C, 54.75; H, 4.97; N, 15.96.
Found: C, 54.65; H, 5.01; N, 16.05.
3,9-Dihydro-9-methoxy-9-phenyl-2H-[1,2,4]oxadiazolo[3,2-
b]quinazolin-2-one (5)
Anal. Calcd for C17H14ClN3O3◊C3H8O (343.77): C, 59.33; H, 5.73;
N, 10.38; Cl, 8.76. Found: C, 59.64; H, 5.39; N, 10.51; Cl, 8.60.
Compound 3a (5.5 g, 17.8 mmol) was heated at 220 °C under re-
duced pressure (0.1 Torr) for 20 min. After cooling under an Ar atm,
9-phenyl-2H-[1,2,4]oxadiazolo[3,2-b]quinazolin-2-one (2a) was
obtained as a yellow solid, which was air sensitive and was used di-
rectly in the next step.
Ethyl 4-Methyl-3-oxidoquinazolin-2-ylcarbamate (3c)
The title compound was prepared as described for 3a, starting from
4c7 (0.75 g, 5.0 mmol) and ethoxycarbonyl isothiocyanate (0.65 g,
5.0 mmol) to give 3c as yellow needles (0.8 g, 65%); mp: 146 °C
(EtOH) (Lit.2 144-146 °C).
IR (KBr): n = 3280, 1770, 1620, 1515, 1270, 1220 cm-1.
1H NMR (300 MHz, CDCl3): d = 1.38 (t, 3H, J = 7.1 Hz), 2.92 (s,
3H), 4.36 (q, 2H, J = 7.1 Hz), 7.52 (m, 1H), 7.73 (m, 1H), 7.81(d,
1H, J = 8.4 Hz), 7.98 (d, 1H, J = 8.3 Hz), 10.08 (s, 1H).
IR (KBr): n = 1805, 1650, 1610, 1480, 1420, 1400, 1360, 1300,
1285, 1240 cm-1.
1H NMR (80 MHz, DMSO-d6): d = 7.05-7.45 (m, 9H).
The crude 2a was dissolved in MeOH (50 mL) and the solution was
refluxed for 45 min and kept overnight at -18 °C. The obtained sol-
id was filtered and dried to give 4.7 g (89%) of 5 as white crystals;
mp: 246 °C.
IR (KBr): n = 3100, 1750, 1630, 1580, 1490 cm-1.
1H NMR (80 MHz, DMSO-d6): d = 3.16 (s, 3H), 7.10-7.40 (m, 9H),
11.66 (br s, 1H).
13C NMR (75 MHz, DMSO-d6): d = 12.9, 14.2, 61.8, 120.7, 124.5,
127.0, 127.1, 132.0, 139.1, 144.4, 150.3, 150.7.
MS (CI+, NH3): m/z = 248 (M+H)+.
Anal. Calcd for C12H13N3O3 (247.26): C, 58.29; H, 5.29; N, 16.99.
Found: C, 58.18; H, 5.32; N, 17.10.
13C NMR (20 MHz, DMSO-d6): d = 50.9, 91.8, 116.5, 120.5, 124.8,
126.4, 127.9, 128.7, 129.2, 130.9, 134.1, 139.4, 161.2, 161.9.
Ethyl 3-Oxidoquinazolin-2-ylcarbamate (3d)
The title compound was prepared as described for 3a, starting from
4d8 (10.0 g, 73.5 mmol) and ethoxycarbonyl isothiocyanate (9.64 g,
73.5 mmol) to give 3d as a white solid (12.4 g, 71%); mp: 142 °C
(EtOAc).
Anal. Calcd for C16H13N3O3 (295.30): C, 65.08; H, 4.44; N, 14.23.
Found: C, 65.12; H, 4.45; N, 14.28.
N-(3-oxido-4-phenylquinazolin-2-yl)-3,6-dihydropyridine-
1(2H)-carboxamide (6)
IR (KBr): n = 3300, 3280, 1770, 1750, 1620, 1520, 1270, 1250
cm-1.
Compound 3a (1 g, 3.2 mmol) was heated at 220 °C under reduced
pressure (0.1 Torr) for 10 min. After cooling under an Ar atm, the
resulting yellow solid (2a) was suspended in a mixture of toluene
(2 mL) and 1,2,3,6-tetrahydropyridine (1 mL), which was refluxed
for 15 min. After cooling, the resulting solution was kept overnight
at r.t. The obtained solid was filtered and dried to give 1.1 g (98%)
of 6 as yellow crystals; mp: 170 °C.
1H NMR (300 MHz, CDCl3): d = 1.38 (t, 3H, J = 7.1 Hz), 4.36 (q,
2H, J = 7.1 Hz), 7.40-8.00 (m, 4H), 8.90 (s, 1H), 9.90 (s, 1H).
13C NMR (75 MHz, CDCl3): d = 14.3, 62.6, 121.1, 124.9, 127.7,
132.7, 139.7, 141.5, 145.7, 150.9.
Anal. Calcd for C11H11N3O3 (233.23): C, 56.65; H, 4.75; N, 18.02.
Found: C, 56.60; H, 4.68; N, 18.18.
IR (KBr): n = 3200, 1700, 1650, 1620, 1580, 1510, 1400, 1300
cm-1.
1H NMR (80 MHz, DMSO-d6): d = 2.20 (m, 2H), 3.60 (t, 2H,
J = 5.5 Hz), 4.05 (m, 2H), 5.80 (m, 2H), 7.20-7.45 (m, 2H), 7.60
(m, 5H), 7.65-7.80 (m, 2H), 9.90 (br s, 1H).
13C NMR (20 MHz, DMSO-d6): d = 24.7, 41.0, 43.9, 120.2, 124.3,
125.2, 125.3, 126.4, 128.6, 129.3, 130.1, 131.7, 140.5, 147.3, 148.8,
151.6.
Ethyl 6-Chloro-3-oxidoquinazolin-2-ylcarbamate (3e)
The title compound was prepared as described for 3a, starting from
4e9 (13.0 g, 76 mmol) and ethoxycarbonyl isothiocyanate (10.0 g,
76 mmol) to give 3e as a white solid (10 g, 49%); mp: 208 °C
(EtOH).
IR (KBr): n = 3270, 1760, 1625, 1530, 1270, 1240 cm-1.
1H NMR (300 MHz, DMSO-d6): d = 1.29 (t, 3H, J = 7.2 Hz), 4.24
(q, 2H, J = 7.2 Hz), 7.78 (m, 2H), 7.98 (d, 1H, J = 0.9 Hz), 9.33 (s,
1H), 10.13 (s, 1H).
MS (CI+, NH3): m/z = 347 (M+H)+, 264 (M-C5H8N)+.
Anal. Calcd for C20H18N4O2 (346.39): C, 69.35; H, 5.24; N, 16.18.
Found: C, 69.27; H, 5.23; N, 16.07.
MS (CI+, NH3): m/z = 268 (M+H)+.
Anal. Calcd for C11H10ClN3O3 (267.67): C, 49.36; H, 3.77; N,
15.70; Cl, 13.25. Found: C, 49.24; H, 3.75; N, 15.62; Cl, 13.20.
3,9-Dihydro-9-phenyl-2H-[1,2,4]oxadiazolo[3,2-b]quinazolin-2-
one (1a)
Compound 3a (5.0 g, 16 mmol) was heated at 220 °C under reduced
pressure (0.1 Torr) for 20 min. After cooling under an Ar atm, the
resulting yellow solid (2a) was dissolved in DMF (10 mL) and
NaBH4 (1.5 g, 40 mmol) was added in portions. The mixture was
stirred for 30 min and poured into H2O (200 mL). The product was
Ethyl 6-Methoxy-3-oxidoquinazolin-2-ylcarbamate (3f)
The title compound was prepared as described for 3a, starting from
4f10 (0.22 g, 1.3 mmol) and ethoxycarbonyl isothiocyanate (0.17 g,
Synthesis 2000, No. 14, 2009–2012 ISSN 0039-7881 © Thieme Stuttgart · New York

2012
P. P. Renaut et al.
PAPER
extracted with EtOAc. The organic layers were washed with H2O,
dried (MgSO4), and concentrated in vacuo to give a crude product
(5.1 g), which was recrystallised in MeOH to give 3.2 g (75%) of 1a
as white crystals; mp: 242 °C.
IR (KBr): n = 3100, 1790, 1660, 1590, 1500 cm-1.
1H NMR (300 MHz, DMSO-d6): d = 6.25 (s, 1H), 6.92 (d, 1H,
J = 7.6 Hz), 7.09 (m, 2H), 7.44-7.30 (m, 6H), 11.90 (br s, 1H).
13C NMR (75 MHz, DMSO-d6): d = 63.0, 116.7, 121.9, 124.4,
127.9, 128.2, 129.2, 129.7, 133.0, 137.4, 163.1, 165.0.
MS (CI+, NH3): m/z = 266 (M+H)+, 283 (M+NH3)+.
1H NMR (80 MHz, DMSO-d6): d = 4.86 (s, 2H), 7.00-7.35 (m, 4H),
11.60 (s, 1H).
MS (CI+, NH3): m/z = 190 (M+H)+, 207 (M+NH3)+.
Anal. Calcd for C9H7N3O2 (189.18): C, 57.14; H, 3.73; N, 22.21.
Found: C, 56.93; H, 3.65; N, 22.19.
7-Chloro-3,9-dihydro-2H-[1,2,4]oxadiazolo[3,2-b]quinazolin-2-
one (1e)
The title compound was prepared as described for 1c, starting from
3e (100 mg, 0.371 mmol) and NaBH4 (17 mg, 0.449 mmol) to give
1e as a white solid (68 mg, 81%); mp: 270 °C (HOAc).
Anal. Calcd for C15H11N3O2 (265.27): C, 67.91; H, 4.18; N, 15.84.
Found: C, 68.00; H, 4.20; N, 15.83.
IR (KBr): n = 1794, 1660, 1584, 1529, 1487, 1390, 1327, 1256,
1159, 1090 cm-1.
1H NMR (300 MHz, DMSO-d6): d = 4.86 (s, 2H), 7.00 (d, 1H,
J = 7.2 Hz), 7.4, (d, 1H, J = 7.2 Hz), 7.42 (s, 1H), 11.75 (s, 1H).
7-Chloro-3,9-dihydro-9-phenyl-2H-[1,2,4]oxadiazolo[3,2-
b]quinazolin-2-one (1b)
The title compound was prepared as described for 1a, starting from
3b (10 g, 30 mmol) and NaBH4 (4.4 g, 110 mmol) to give 1b as a
white solid (6.8 g, 75%); mp: 254 °C (DMF/H2O).
Anal. Calcd for C9H6ClN3O2 (223.62): C, 48.34; H, 2.70; N, 18.79.
Found: C, 47.90; H, 2.57; N, 18.48.
IR (KBr): n = 3100, 3050, 1770, 1640, 1580, 1480 cm-1.
1H NMR (80 MHz, DMSO-d6): d = 6.28 (s, 1H), 7.01 (d, 1H, J = 2.7
Hz), 7.14 (d, 1H, J = 8.2 Hz), 7.20-7.55 (m, 6H), 11.20 (br s, 1H).
13C NMR (20 MHz, DMSO-d6): d = 62.6, 118.5, 123.9, 127.8,
128.0, 129.4, 129.7, 132.3, 136.8, 162.9, 164.8.
MS (CI+, NH3): m/z = 300 (M+H)+, 317 (M+NH3)+.
3,9-Dihydro-7-methoxy-2H-[1,2,4]oxadiazolo[3,2-b]quinazolin-
2-one (1f)
The title compound was prepared as described for 1c, starting from
3f (100 mg, 0.38 mmol) and NaBH4 (17 mg, 0.448 mmol) to give 1f
as a white solid (70 mg, 84%); mp: 221 °C.
IR (KBr): n = 1792, 1654, 1587, 1560, 1506, 1407, 1337, 1286,
1240, 1171, 1122, 1036 cm-1.
1H NMR (300 MHz, DMSO-d6): d = 3.73 (s, 3H), 4.80 (s, 2H), 6.92
(m, 3H), 11.49 (s, 1H).
Anal. Calcd for C15H10ClN3O2 (299.72): C, 60.11; H, 3.36; N,
14.02; Cl, 11.83. Found: C, 60.03; H, 3.41; N, 14.08; Cl, 11.98.
Anal. Calcd for C10H9N3O3 (219.20): C, 54.79; H, 4.14; N, 19.17.
Found: C, 54.74; H, 3.99; N, 18.94.
3,9-Dihydro-9-methyl-2H-[1,2,4]oxadiazolo[3,2-b]quinazolin-
2-one (1c)
To a solution of 3c (63 mg, 0.255 mmol) in EtOH (5 mL) was added
NaBH4 (13 mg, 0.34 mmol).The resulting solution was stirred at r.t.
for 2 h and at 50 °C for 6 h. The solvent was then removed in vacuo
and the residue was taken into 5% KHSO4 (10 mL). The resulting
suspension was filtered. The solid was washed with the KHSO4 so-
lution, twice with H2O, and dried to give 53 mg of 1c (100%); mp:
252-253 °C (EtOH).
IR (KBr): n = 2795, 1765, 1640, 1490, 1160, 880, 750 cm-1.
1H NMR (300 Hz, CDCl3): d = 1.62 (d, 3H, J = 6.3 Hz), 5.09 (q, 1H,
J = 6.3 Hz), 7.14 (m, 2H), 7.26 (m, 1H), 7.37 (m, 1H), 12.24 (br s,
1H).
References
(1) Katritzky, A. R. J. Chem. Soc. 1956, 2063.
For a related reaction, see: Muller, J.-C.; Ramuz, H.; Dally, J.;
Schoenholzer, P. Helv. Chim. Acta 1982, 65, 1454.
(2) Kadunc, Z.; Stanovnik, B.; Tisler, M. Vestn. Slov. Kem. Drus.
1984, 31, 23.
(3) Sim, T. B.; Ahn, J. H.; Yoon, N. M. Synthesis 1996, 3, 324.
(4) Maeda, H.; Selvakumar, N.; Kraus, G. A. Tetrahedron 1999,
55, 943.
Bartoli, G.; Marcantoni, E.; Petrini, M. J. Chem. Soc., Chem.
Commun. 1991, 12, 793.
Abalain, C.; Langlois, M. Eur. J. Med. Chem. 1998, 33, 155.
(5) Auwers, K.; Jordan, O. Chem. Ber. 1924, 57B, 800.
(6) Sternbach, L. H.; Kaiser, S.; Reeder, E. J. Am. Chem. Soc.
1960, 82, 475.
13C NMR (75 MHz, CDCl3): d = 18.5, 56.6, 117.3, 121.9, 124.9,
128.4, 130.0, 131.9, 162.2, 163.9.
MS (CI+, NH3): m/z = 204 (M+H)+, 221 (M+NH3)+.
Anal. Calcd for C10H9N3O2 (203.20): C, 59.11; H, 4.46; N, 20.68.
Found: C, 58.98; H, 4.48; N, 20.46.
(7) Busch, M.; Strätz, A. J. Prakt. Chem. 1937, 150, 1.
(8) Schwan, T. J.; Davis, C. S. J. Pharm. Sci. 1968, 57, 877.
(9) Ostrowski, S. Heterocycles 1996, 43, 389.
(10) Brown, D. J.; England, B. T. Isr. J. Chem. 1968, 6, 569.
3,9-Dihydro-2H-[1,2,4]oxadiazolo[3,2-b]quinazolin-2-one (1d)
The title compound was prepared as described for 1c, starting from
3d (1.05 g, 4.5 mmol) and NaBH4 (0.17 g, 4.5 mmol) to give 1d as
a white solid (0.74 g, 86%); mp: 252 °C (EtOH).
Article Identifier:
1437-210X,E;2000,0,14,2009,2012,ftx,en;H05200SS.pdf
IR (KBr): n = 3100, 1790, 1650, 1600, 1500 cm-1.
Synthesis 2000, No. 14, 2009–2012 ISSN 0039-7881 © Thieme Stuttgart · New York