A concise synthesis of 4-imino-3,4-dihydroquinazolin-2-ylphosphonates via a palladium-catalyzed reaction of carbodiimide, isocyanide, and phosphite

Article abstract of DOI:10.1039/c2ob26979a

A palladium-catalyzed reaction of 2-iodoarylcarbodiimide, isocyanide, and phosphite leads to 4-imino-3,4-dihydroquinazolin-2-ylphosphonates in moderate to good yields. Three bonds are formed in a one pot procedure and the tandem process includes nucleophilic attack, isocyanide insertion, and C-N coupling. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c2ob26979a

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A concise synthesis of 4-imino-3,4-dihydroquinazolin-
2-ylphosphonates via a palladium-catalyzed reaction
of carbodiimide, isocyanide, and phosphite†
Cite this: Org. Biomol. Chem., 2013, 11,
798
Guanyinsheng Qiu,‡a Yuan Lu‡b and Jie Wu*a,c
Received 11th October 2012,
Accepted 16th November 2012
A
palladium-catalyzed reaction of 2-iodoarylcarbodiimide, isocyanide, and phosphite leads to
4-imino-3,4-dihydroquinazolin-2-ylphosphonates in moderate to good yields. Three bonds are formed
in a one pot procedure and the tandem process includes nucleophilic attack, isocyanide insertion, and
C–N coupling.
DOI: 10.1039/c2ob26979a
www.rsc.org/obc
Recently, palladium-catalyzed isocyanide insertion has
1. Introduction
been developed as an efficient route to N-heterocycles.6 For
The importance of organophosphorus compounds is well instance, 4-aminophthalazin-1(2H)-ones could be synthesized
recognized due to their ubiquity in biological systems.1 Recent via a palladium-catalyzed cross-coupling of o-(pseudo)halo-
studies have revealed that many heterocycles containing phos- benzoates and hydrazines with isocyanide insertion followed
phorus showed excellent bioactivities. For example, phospha- by lactamization.6h Inspired by the attractiveness of the chem-
coumarins showed good inhibitory activity against SHP-1.2a istry of palladium-catalyzed isocyanide insertion, we conceived
Phosphonylated isoindoles displayed promising activity as that phosphonylated quinazolines could be produced through
HCT-116 (human colon cancer cells) inhibitors.2b In light of a palladium-catalyzed reaction of carbodiimide 1,7 phosphite
the importance of phosphonylated compounds, we are inter- 2, and isocyanide 3. The proposed synthetic route is presented
ested in the method development for the generation of phos- in Scheme 1. A nucleophilic addition of phosphite 2 to carbo-
phonylated heterocycles and their focused libraries.
diimide 1 would take place to afford compound A. The sub-
N-Heterocyclic compounds with privileged scaffolds are of sequent transformation would involve oxidative addition of
continued interest in organic chemistry, especially in studies Pd(0) to compound A giving Pd(II) species B, which would then
of chemical genetics.3 In the past few years, we have been undergo an insertion process with isocyanide 3 to afford
involved in the generation of natural product-like compounds
for different biological evaluations.4 Since quinazoline deriva-
tives show a broad range of biological properties including
anti-microbial, antidepressant, and anti-infective activities,5
we envisioned that the phosphonylated quinazolines would be
beneficial for the subsequent biological assays. Therefore, we
initiated a program to explore the possibility for the formation
of phosphonylated quinazolines.
aDepartment of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433,
China. E-mail: jie_wu@fudan.edu.cn; Fax: +86 21 6564 1740;
Tel: +86 21 6510 2412
bObstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai
200011, China
cState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
†Electronic supplementary information (ESI) available: Experimental procedure,
characterization data, CIF of compound 4i, 1H and 13C NMR spectra of
compounds 4. CCDC 901494. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c2ob26979a
‡Author contributions: G. Qiu and Y. Lu contributed equally.
Scheme 1 A proposed synthetic route to phosphonylated quinazolines.
798 | Org. Biomol. Chem., 2013, 11, 798–802
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intermediate C. Then phosphonylated quinazoline 4 would be was added (Table 1, entry 8). The presence of base was essential
formed through the following reductive elimination with for the successful conversion (Table 1, entry 11). Evaluation of
regeneration of the Pd(0) catalyst concurrently. This strategy bases showed that cesium carbonate was the best choice
would be attractive since three bonds could be formed in a (Table 1, entries 12–15). No improvement was observed when
one-pot procedure. Therefore, we started to investigate this the reaction was performed in other solvents (Table 1, entries
proposed palladium-catalyzed multicomponent reaction.8
16–19). The efficiency was affected when the amount of palla-
dium catalyst was reduced to 5 mol% (Table 1, entry 20).
We next explored the scope of this palladium-catalyzed reac-
tion of 2-iodoarylcarbodiimides 1, phosphite 2, and isocya-
nides 3 under the optimized conditions (10 mol% of Pd(OAc)2,
10 mol% of FeCl3, 10 mol% of DPPF, 3.0 equiv. of Cs2CO3,
toluene, reflux). The results are summarized in Table 2.
Different 2-iodoarylcarbodiimides 1 were examined and a
2. Results and discussion
A model reaction of bis-(2-iodophenyl)carbodiimide 1a, diethyl
phosphite 2a, and tert-butyl isocyanide 3a was studied
(Table 1). The reaction was complex catalyzed by 10 mol% of
palladium acetate in the presence of cesium carbonate in
toluene under reflux (Table 1, entry 1). The reaction failed
when triphenylphosphine was added as a ligand (Table 1,
entry 2). Gratifyingly, the desired product 4a was furnished in
19% yield when PCy3 was employed (Table 1, entry 3). Other
ligands including phosphines and NHC were screened in the
meantime. To our delight, the expected phosphonylated quin-
azoline 4a was obtained in 43% yield when DPPF was utilized
as the ligand in the reaction (Table 1, entry 4). Since the pres-
ence of Lewis acid would promote the nucleophilic addition of
phosphite to bis-(2-iodophenyl)carbodiimide, several metal
salts as additives were examined (Table 1, entries 8–10). The
yield was increased to 57% when 10 mol% of iron(III) chloride
range of 4-imino-3,4-dihydroquinazolin-2-ylphosphonates
4
was produced as expected. 2-Iodoarylcarbodiimides 1 with an
aryl or alkyl group at the R2 position were all good substrates
during the transformation. For instance, N-((2-iodophenyl-
imino)methylene)-4-methylbenzenamine reacted with diethyl
Table 2 Synthesis of 4-imino-3,4-dihydroquinazolin-2-ylphosphonates
via
a palladium-catalyzed reaction of carbodiimide, isocyanide, and
phosphitea
Table 1 Initial studies for the palladium-catalyzed reaction of carbodiimide 1a,
diethyl phosphite 2a, and tert-butyl isocyanide 3aa
Entry Ligand
Additive
Base
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
—
PPh3
PCy3
DPPF
Xant-phos
Xphos
IPr
DPPF
DPPF
DPPF
DPPF
DPPF
DPPF
DPPF
DPPF
DPPF
DPPF
DPPF
DPPF
DPPF
—
—
—
—
—
—
—
FeCl3
BiCl3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Complex
Trace
19
43
41
Complex
Complex
57
53
27
Complex
Trace
44
19
32
9
10
11
12
13
14
15
16
17
18
19
20c
Sc(OTf)3 Cs2CO3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
—
KOAc
K3PO4
NaHCO3 Toluene
tBuOK
Toluene
DMF
1,4-Dioxane 29
MeCN
DCE
Toluene
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Complex
41
Complex
37
a Reaction conditions: carbodiimide 1a (1.0 equiv.), isocyanide 2a (2.0
equiv.), diethyl phosphite 3a (2.0 equiv.), palladium catalyst (10 mol%),
ligand (10 mol%), base (3.0 equiv.), additive (10 mol%), reflux.
b Isolated yield based on carbodiimide 1a. c In the presence of Pd-
(OAc)2 (5 mol%).
a Isolated yield based on 2-iodoarylcarbodiimide 1.
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mixture was stirred at reflux. After completion of reaction as
indicated by TLC (8–12 h), the solvent was evaporated and the
residue was purified on silica gel to provide the desired
product 4.
Diethyl (E)-4-(tert-butylimino)-3,4-dihydro-3-(2-iodophenyl)-
quinazolin-2-yl-2-phosphonate (4a). 1H NMR (400 MHz,
CDCl3) δ 1.14 (t, J = 7.2 Hz, 3H), 1.23 (s, 9H), 1.36 (t, J = 7.2 Hz,
3H), 3.66–3.71 (m, 1H), 3.72–3.93 (m, 1H), 4.22–4.28 (m, 2H),
7.01–7.06 (m, 1H), 7.41–7.61 (m, 5H), 7.86 (d, J = 8.0 Hz, 1H),
7.98 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 16.1,
16.3, 31.0, 53.0, 63.0, 64.6, 102.6, 122.3, 125.8, 127.9, 128.8,
128.9, 129.6, 131.6, 132.9, 138.5, 142.6, 146.5, 151.8; HRMS
Calcd for C22H28IN3O3P+ (ESI, M + H+): 540.0907; found:
540.0920.
Diethyl (E)-4-(tert-butylimino)-3,4-dihydro-3-phenylquinazo-
lin-2-yl-2-phosphonate (4b). 1H NMR (400 MHz, CDCl3) δ 1.14
(t, J = 7.2 Hz, 3H), 1.23 (s, 9H), 1.36 (t, J = 7.2 Hz, 3H),
3.66–3.70 (m, 1H), 3.87–3.91 (m, 1H), 4.24–4.28 (m, 2H),
6.90–6.94 (m, 1H), 7.05–7.28 (m, 7H), 7.61 (d, J = 8.0 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 16.1, 16.3, 31.0, 53.0, 62.9, 64.6,
121.1, 122.9, 123.1, 123.7, 124.2, 127.5, 128.6, 130.8 141.9,
145.6, 148.1, 153.6; HRMS Calcd for C22H29N3O3P+ (ESI, M + H+):
414.1941; found: 414.1940.
Diethyl (E)-4-(tert-butylimino)-3,4-dihydro-3-p-tolylquinazo-
lin-2-yl-2-phosphonate (4c). 1H NMR (400 MHz, CDCl3) δ 1.12
(t, J = 7.2 Hz, 3H), 1.22 (s, 9H), 1.35 (t, J = 7.2 Hz, 3H), 2.40 (s,
3H), 3.64–3.70 (m, 1H), 3.85–3.93 (m, 1H), 4.23–4.26 (m, 2H),
7.00–7.03 (m, 1H), 7.24–7.41 (m, 3H), 7.60 (d, J = 8.0 Hz, 2H),
7.84 (d, J = 8.0 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 16.3, 16.5, 20.2, 31.2, 53.1, 63.2, 63.9,
122.5, 126.2, 128.9, 129.3, 129.8, 131.8, 133.2, 138.7, 142.8,
146.9, 149.5, 152.0; HRMS Calcd for C23H31N3O3P+ (ESI, M + H+):
428.2098; found: 428.2135.
Fig. 1 X-ray ORTEP illustration of 4-imino-3,4-dihydroquinazolin-2-ylphospho-
nate 4i (30% probability ellipsoids).
phosphite and tert-butyl isocyanide, leading to the desired
product 4c in 78% yield. Reactions of dipropyl phosphite were
explored as well, which gave rise to the corresponding pro-
ducts in moderate to good yields. Other isocyanides were tried
in the meantime. Reactions employing cyclohexyl isocyanide
or n-butyl isocyanide were all workable. However, aryl isocya-
nide was not a good partner in the palladium-catalyzed reac-
tion of carbodiimide 1 with phosphite 2. For example, only a
trace amount of product 4o was detected when 2,6-dimethyl-
phenyl isocyanide was employed in the reaction. In the
meantime, the structural elucidation of 4-imino-3,4-dihydro-
quinazolin-2-ylphosphonate 4i was demonstrated by X-ray
diffraction analysis (Fig. 1).
Diethyl
(E)-4-(tert-butylimino)-3-(4-chlorophenyl)-3,4-di-
3. Conclusion
hydroquinazolin-2-yl-2-phosphonate (4d). 1H NMR (400 MHz,
CDCl3) δ 1.12 (t, J = 7.2 Hz, 3H), 1.21 (s, 9H), 1.34 (t, J = 7.2 Hz,
3H), 3.64–3.70 (m, 1H), 3.85–3.89 (m, 1H), 4.23–4.26 (m, 2H),
7.00–7.04 (m, 1H), 7.22–7.41 (m, 3H), 7.50–7.54 (m, 1H), 7.60
(d, J = 8.0 Hz, 1H), 7.84 (d, J = 7.6 Hz, 1H), 7.97 (d, J = 8.4 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 16.1, 16.3, 31.0, 53.0, 62.9,
64.6, 122.3, 126.1, 128.1, 128.8, 129.1, 129.7, 131.2, 132.9,
138.5, 146.5, 149.2, 151.8; HRMS Calcd for C22H28ClN3O3P+
(ESI, M + H+): 448.1551; found: 448.1553.
In conclusion, we have described a concise synthesis of
4-imino-3,4-dihydroquinazolin-2-ylphosphonates via a palla-
dium-catalyzed reaction of 2-iodoarylcarbodiimide, isocyanide,
and phosphite. Three bonds are formed in a one pot procedure
and the tandem process includes nucleophilic attack, isocya-
nide insertion, and C–N coupling. Currently, library construc-
tion and the biological evaluations of these compounds are
under investigation in our laboratory.
Diethyl (E)-4-(tert-butylimino)-3-butyl-3,4-dihydroquinazo-
lin-2-yl-2-phosphonate (4e). 1H NMR (400 MHz, CDCl3) δ 0.94
(t, J = 7.2 Hz, 3H), 1.25–1.38 (m, 8H), 1.41 (s, 9H), 1.55–1.62
(m, 2H), 4.29–4.36 (m, 6H), 7.25–7.27 (m, 1H), 7.46–7.48
(m, 2H), 7.93 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3)
δ 14.0, 16.3, 16.3, 20.3, 30.1, 31.7, 46.5, 53.3, 64.0, 64.1, 121.2,
125.2, 127.8, 129.3, 131.1, 146.8, 149.8, 152.4; HRMS Calcd for
4. Experimental section
General procedure of the synthesis of 4-imino-3,4-
dihydroquinazolin-2-ylphosphonates via a palladium-catalyzed
reaction of carbodiimide, isocyanide, and phosphite
Pd(OAc)2 (10 mol%), DPPF (10 mol%), and FeCl3 (10 mol%) C20H33N3O3P+ (ESI, M + H+): 394.2254; found: 394.2265.
were added to a solution of carbodiimides 1 (0.2 mmol) in Diethyl (E)-4-(tert-butylimino)-3-benzyl-3,4-dihydroquinazo-
toluene (2.0 mL) under N2 atmosphere at room temperature. lin-2-yl-2-phosphonate (4f). 1H NMR (400 MHz, CDCl3)
Then phosphite 2 (1.5 equiv.) was added. After the mixture δ 1.26–1.37 (m, 15H), 4.22–4.24 (m, 4H), 5.53 (s, 2H), 7.15–7.27
was stirred at room temperature for 1 hour, isocyanide 3 (m, 6H), 7.49–7.53 (m, 2H), 7.84 (d, J = 7.6 Hz, 1H); 13C NMR
(2.0 equiv.) and Cs2CO3 (2.0 equiv.) was added. Then the (100 MHz, CDCl3) δ 16.0, 31.3, 49.6, 53.2, 64.1, 121.4, 125.4,
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126.2, 127.1, 127.7, 127.8, 129.2, 131.2, 138.3, 150.2, 152.7; 126.1, 127.2, 127.6, 129.2, 131.1, 138.5, 139.5, 146.5, 153.3;
HRMS Calcd for C23H31N3O3P+ (ESI, M + H+): 428.2098; found: HRMS Calcd for C25H35N3O3P+ (ESI, M + H+): 456.2411; found:
428.2098.
456.2413.
Diethyl (E)-4-(tert-butylimino)-3-cyclohexyl-3,4-dihydroquin-
Diethyl (E)-3-butyl-4-(cyclohexylimino)-3,4-dihydroquinazo-
azolin-2-yl-2-phosphonate (4g). 1H NMR (400 MHz, CDCl3) lin-2-yl-2-phosphonate (4m). 1H NMR (400 MHz, CDCl3) δ 0.94
δ 1.38–1.41 (m, 17H), 1.78–1.86 (m, 6H), 2.72–2.78 (m, 2H), (t, J = 6.4 Hz, 3H), 1.25–1.45 (m, 15H), 1.81–1.83 (m, 5H),
4.29–4.33 (m, 5H), 7.18–7.20 (m, 1H), 7.40–7.41 (m, 2H), 7.72 4.03–4.05 (m, 1H), 4.30–4.33 (m, 6H), 7.26–7.26 (m, 1H),
(d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 16.3, 16.4, 7.48–7.51 (m, 2H), 7.78 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz,
25.9, 26.8, 30.7, 31.7, 31.9, 54.3, 63.3, 64.0, 64.1, 122.1, 124.7, CDCl3) δ 13.9, 16.3, 16.4, 20.3, 24.4, 26.1, 29.9, 35.0, 46.5, 56.3,
126.6, 128.4, 130.8, 146.7, 150.4, 152.9; HRMS Calcd for 64.1, 64.1, 120.8, 126.1, 127.3, 128.3, 131.3, 146.2, 149.3, 151.9;
C22H34N3NaO3P+ (ESI, M + Na+): 442.2230; found: 442.2248.
HRMS Calcd for C22H35N3O3P+ (ESI, M + H+): 420.2411; found:
Diethyl (E)-4-(tert-butylimino)-3,4-dihydro-3-(2-iodo-4-methyl- 420.2414.
phenyl)-6-methylquinazolin-2-yl-2-phosphonate (4h). 1H NMR
Diethyl (E)-3-benzyl-4-(butylimino)-3,4-dihydroquinazolin-
(400 MHz, CDCl3) δ 1.14 (t, J = 7.2 Hz, 3H), 1.23 (s, 9H), 1.36 2-yl-2-phosphonate (4n). 1H NMR (400 MHz, CDCl3) δ 0.82 (t, J
(t, J = 7.2 Hz, 3H), 2.41 (s, 3H), 2.45 (s, 3H), 3.66–3.70 (m, 1H), = 7.6 Hz, 3H), 1.20–1.28 (m, 8H), 1.47–1.54 (m, 2H), 3.68–3.71
3.87–3.91 (m, 1H), 4.24–4.28 (m, 2H), 7.10 (d, J = 8.0 Hz, 1H), (m, 2H), 4.20–4.27 (m, 4H), 5.63 (s, 2H), 7.14–7.31 (m, 6H),
7.33–7.35 (m, 2H), 7.60 (d, J = 7.6 Hz, 1H), 7.87 (s, 1H), 7.93 7.50–7.54 (m, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 8.0 Hz,
(s, 1H); 13C NMR (100 MHz, CDCl3) δ 16.1, 16.3, 20.6, 20.6, 1H); 13C NMR (100 MHz, CDCl3) δ 13.8, 15.9, 16.0, 20.2, 35.1,
31.0, 52.9, 63.0, 64.6, 122.3, 126.0, 128.1, 128.7, 128.8, 129.1, 49.3, 50.4, 64.0, 64.1, 121.6, 126.0, 126.3, 126.9, 127.7, 128.3,
129.7, 131.7, 133.0, 138.6, 140.4, 142.6, 146.5; HRMS Calcd for 131.4, 138.0, 143.5, 135.9; HRMS Calcd for C23H31N3O3P+ (ESI,
C24H32IN3O3P+ (ESI, M + H+): 568.1220; found: 568.1220.
M + H+): 428.2098; found: 428.2111.
Diethyl
(E)-4-(tert-butylimino)-6-chloro-3-(4-chloro-2-iodo-
Financial support from the National Natural Science Foun-
phenyl)-3,4-dihydroquinazolin-2-yl-2-phosphonate
(4i). 1H dation of China (nos. 21032007, 21172038) is gratefully
NMR (400 MHz, CDCl3) δ 1.16 (t, J = 7.2 Hz, 3H), 1.23 (s, 9H), acknowledged.
1.36 (t, J = 7.2 Hz, 3H), 3.78–3.82 (m, 1H), 3.92–3.98 (m, 1H),
4.22–4.26 (m, 2H), 7.31 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.0 Hz,
1H), 7.48–7.52 (m, 2H), 7.83 (s, 1H), 7.93 (s, 1H); 13C NMR
Notes and references
(100 MHz, CDCl3) δ 16.0, 16.2, 30.9, 53.2, 63.2, 63.7, 102.5,
122.9, 128.2, 129.2, 130.0, 131.6, 131.9, 133.4, 133.9, 137.8, 1 For examples: (a) F. H. Westheimer, Science, 1987, 235, 1173;
139.1, 140.9, 144.8, 151.7; HRMS Calcd for C22H26Cl2IN3O3P+
(ESI, M + H+): 608.0128; found: 608.0122.
(b) H. Seto and T. Kuzuyama, Nat. Prod. Rep., 1999, 16, 589;
(c) P. Kafarski and B. LeJczak, Curr. Med. Chem.: Anti-Cancer
Agents, 2001, 1, 301; (d) O. M. Colvin, Curr. Pharm. Des.,
1999, 5, 555; (e) M. M. Mader and P. A. Bartlett, Chem. Rev.,
1997, 97, 1281; (f) A. P. Kaplan and P. A. Bartlett, Biochemis-
try, 1991, 30, 8165; (g) S. A. Beers, C. F. Schwender,
D. A. Loughney, E. Malloy, K. Demarest and J. Jordan,
Bioorg. Med. Chem., 1996, 4, 1693.
Diethyl (E)-4-(tert-butylimino)-3-(2-bromo-4-methylphenyl)-
3,4-dihydro-6-methylquinazolin-2-yl-2-phosphonate (4j). 1H NMR
(400 MHz, CDCl3) δ 1.14 (t, J = 7.2 Hz, 3H), 1.23 (s, 9H), 1.36
(t, J = 7.2 Hz, 3H), 2.40 (s, 3H), 2.44 (s, 3H), 3.76–3.79 (m, 1H),
3.87–3.91 (m, 1H), 4.31–4.38 (m, 2H), 7.09 (d, J = 7.6 Hz, 1H),
7.27–7.33 (m, 2H), 7.60 (d, J = 8.0 Hz, 1H), 7.86 (s, 1H), 7.95
(s, 1H); 13C NMR (100 MHz, CDCl3) δ 16.3, 16.5, 20.6, 21.3, 2 For selected examples, see: (a) X. S. Li, D. W. Zhang,
31.2, 53.5, 63.4, 65.0, 102.8, 123.3, 128.5, 129.5, 130.3, 131.9,
132.2, 133.7, 134.2, 138.2, 141.3, 152.1; HRMS Calcd for
C24H32BrN3O3P+ (ESI, M + H+): 520.1359; found: 520.1359.
H. Pang, F. Shen, H. Fu, Y. Y. Jiang and Y. F. Zhao, Org. Lett.,
2005, 7, 4919; (b) X. Yu, Q. Ding and J. Wu, J. Comb. Chem.,
2010, 12, 743.
Dipropyl (E)-4-(tert-butylimino)-3-butyl-3,4-dihydroquinazo- 3 (a) D. P. Walsh and Y.-T. Chang, Chem. Rev., 2006, 106, 2476;
lin-2-yl-2-phosphonate (4k). 1H NMR (400 MHz, CDCl3) δ 0.94
(t, J = 7.6 Hz, 3H), 1.38–1.49 (m, 23H), 1.68–1.73 (m, 2H), 4.27
(t, J = 7.2 Hz, 2H), 4.87–4.91 (m, 2H), 7.23–7.26 (m, 1H),
7.43–7.47 (m, 2H), 7.91 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 14.0, 20.3, 23.7, 23.7, 24.2, 24.2, 29.6, 31.8, 46.5, 53.3,
121.2, 125.0, 127.6, 129.3, 131.1, 146.9, 150.4, 152.9; HRMS
Calcd for C22H37N3O3P+ (ESI, M + H+): 422.2567; found:
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802 | Org. Biomol. Chem., 2013, 11, 798–802
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