Synthesis and antibacterial activity of new diaryldiamines

Article abstract of DOI:10.1002/jhet.1040

Several new quinolines and quinazolines (4, 10, 13) have been synthesized from cheap and readily available chemicals through a series of simple chemical transformations. Most of the synthesized compounds have been evaluated for antibacterial activity against Gram positive and Gram negative strains. Some of the synthesized compounds displayed interesting activity but not very promising for further development.

Full text of DOI:10.1002/jhet.1040

November 2012
Synthesis and Antibacterial Activity of New Diaryldiamines
1391
a
b
b
a
*
Farhana Samrin, Akash Sharma, Inshad Ali Khan, and Sadhna Puri
aDepartment of Chemistry, Dayanand Girls Post Graduate College, Kanpur 208001, India
bClinical Microbiology Unit, Indian Institute of Integrative Medicine (CSIR)
(Formerly Regional Research laboratory), Jammu Tawi 180001, India
*
E-mail: psadhna55@yahoo.com
Received April 12, 2011
DOI 10.1002/jhet.1040
View this article online at wileyonlinelibrary.com.
Several new quinolines and quinazolines (4, 10, 13) have been synthesized from cheap and readily
available chemicals through a series of simple chemical transformations. Most of the synthesized
compounds have been evaluated for antibacterial activity against Gram positive and Gram negative
strains. Some of the synthesized compounds displayed interesting activity but not very promising for
further development.
J. Heterocyclic Chem., 49, 1391 (2012).
INTRODUCTION
quinoline 1 with excess of 1,3-diaminopropane followed
by deprotection of 4-methoxybenzyl group and reductive
alkylation of the resulting intermediates 4-quinolones 3
with 1,3-diaryl-1H-pyrazole-4-carbaldehydes (Scheme 1).
The precursor 1 was prepared by refluxing aniline and
malonic acid in phosphorousoxy chloride followed by
para-methoxybenzyl (PMB) protection in basic condition
according to the literature procedures [8], [12]. The other
precursor 1,3-diaryl-1H-pyrazole-4-carbaldehydes 3’ were
prepared [14] in two step from condensation reaction of
arylmethylketones and phenylhydrazine in ethanol followed
by cyclization of phenylhydrazone with phosphorousoxy
chloride in excellent yields.
Quinazolone 10a–f the other class of target compounds
were synthesized from the reaction of 2-chloro-4-quinazolone
(8) and 1,3-diaminopropane followed by reductive alkylation
with suitable aldehydes. The intermediate 8 was synthesized
in three steps [13] (Scheme 2).
Quinolone derivative (13a) has been synthesized in
three steps by nucleophilic substitution reaction of 2-chloro-
4-(4-methoxybenzyloxy)quinoline (1) with diamine (18)
followed by deprotection of the 4-methoxybenzyloxy
(PMB) group to provide 4-quinolone derivative 12a, which
on reductive alkylation with 3,4-dichlorobenzaldehyde in
alkaline medium afforded compound 13a (Scheme 3).
Similarly compound 13b was obtained from reaction
of 2-chloroquinoline 1 and diamine 22 followed by
deprotection of PMB group and reductive alkylation with
3,4-dichlorobenzaldehyde (Scheme 3).
Quinoline being present in the core structure of many
natural [1,2] and biologically active products [3,4] has been
attracting considerable interests of synthetic and medicinal
chemists. Quinoline derivatives particularly containing
4-quinolones (Figure 1) in their molecular structure have
been effectively used as antibacterial agents for past 35
years. The antibacterial activity of quinolones having
3-carboxylic acid functionality display by inhibiting nucleic
acid synthesis [5] while 2-amino-4-quinolone [6] act by
inhibiting protein synthesis [7] in bacteria (Figure 1). The
second class of quinolones has recently been discovered
[8] as inhibitors of methionyl-tRNA synthetase enzyme
which is a promising antibacterial drug target. This class of
compounds have also been reported [9,10] to display signif-
icant antibacterial activity in the strains of Staphylococcus
areus, Entrococcus faecalis and Entrococcus faecium. How-
ever, the emergence of drug resistance against existing anti-
biotics still demands for the synthesis of new antibacterial
agents. Herein, we report synthesis and antibacterial activi-
ties of pyrazol-4-yl linked quinolones compounds (4), aryl
quinazolone compounds (10), and quinolone-arene (13).
We envisioned synthesizing quinolones-pyrazoles hybrid
structures because quinazolone [8] and pyrazole [11] are
known for antibacterial properties but their hybrid structures
have not been evaluated for antibacterial activity.
RESULTS AND DISCUSSION
Chemistry. The targets compounds 4a-l were synthesized in
three step by amination of 2-chloro-4-(4-methoxybenzyloxy)
Diamine (18) required for preparation of compound
13a has been synthesized from 1,3-dibromopropan-2-ol
© 2012 HeteroCorporation

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F. Samrin, A. Sharma, I. A. Khan, and S. Puri
Vol 49
Scheme 2. Reagents and conditions: (i) Fuse, 190ꢀC, 1 h, yield 95%;
(ii) POCl3, reflux, 5 h, yield 92%; (iii) 1N NaOH, rt, 3 h, yield 92%;
(iv) 1,3-diaminopropane, 70ꢀC, 48 h, yield 80%; (v) suitable aldehyde,
MeONa, NaCNBH3, MeOH, 50ꢀC, 6 h.
Figure 1. Structure of quinolone drugs.
(Scheme 4). 1,3-Dibromopropan-2-ol (14) on treatment
with sodium azide in DMF at 80ꢀC provided diazide 15
which on allylation with allyl bromide in presence cesium
hydroxide afforded compound 16. The olefin of compound
16 was conveniently transformed into dihydroxy derivative
(17) which on azide reduction with 10% Pd-C provided
diamine 18 as racemic mixture in overall very good yield
(Scheme 4).
The intermediate 16 was further transformed into the
diamine 22 (Scheme 5). Compound 16 was converted to
epoxide 19 with mCPBA which on aminolysis with
aqueous ammonia followed by Boc-protection afforded
intermediate 21. Compound 21 on Pd-catalyzed hydroge-
nation in hydrogen atmosphere formed diamine 22 in
quantitative yield (Scheme 5).
Biology. Antibacterial activity of all the synthesized
compounds was performed using microdilution method
(CLSI M7-A8 2009) against three Gram positive strains
(S. aureus ATCC 29213, Methicillin resistant S. aureus,
Vancomycin resistant Enterococcus faecalis), and two
Gram negative strains (Escherichia coli ATCC 25922,
Pseudomonas aeruginosa ATCC 27853), Table 1. Bacterial
suspensions were prepared in sterile normal saline from
24 h grown culture. The Minimum Inhibitory Concentration
(MIC) was performed in Muller Hinton Broth (MHB; BD
Biosciences). Two-fold serial dilutions of samples were
prepared in MHB in 100 mL volume in a 96 well U
bottom microtiter plates (Tarson, Mumbai, India). The final
concentration of the samples ranged from 0.5 to 256 mg/mL.
The turbidity of bacterial suspensions was adjusted to 0.5
McFarland (∼ 1.5 Â 108 CFU/mL), which was further
diluted in MHB and, a 100-mL volume of this diluted
inoculum was added to each well of the plate, resulting in a
final inoculum of 5 Â 106 CFU/mL. The plates were
incubated at 37ꢀC for 24 h and were read visually. The
minimum concentration of the sample showing no turbidity
was recorded as MIC.
Scheme 1. Reagents and conditions: (i) 2a: 1,3-diaminopropane, 90ꢀC,
48 h, yield 72%; 2b: 1,3-diaminopropan-2-ol, K2CO3, DMSO, 80ꢀC,
48 h, yield 55%; (ii) 20% TFA-DCM, rt, 2 h; (iii) 1,3-diaryl-1H-pyrazole-
4-carbaldehydes 3’, MeONa, NaCNBH3, MeOH, 50ꢀC, 6 h.
These compounds were also evaluated against Candida
albicans and Aspergillus fumigatus for antifungal activity
but none of these compounds displayed significant activity.
EXPERIMENTAL
N1-(4-(4-Methoxybenzyloxy)quinolin-2-yl)propane-1,3-diamine
(2a). A mixture of 1 (15.0 g, 50 mmol) and 1,3-diaminopropane
(20 mL) was stirred at 80–90ꢀC for 48 h. The excess of 1,
3-diaminopropane was evaporated and crude product obtained was
purified on silica gel column chromatography using CH2Cl2/MeOH/
NH3 sol (90:10:0.5) as eluent. 1H NMR (CD3OD, 300 MHz)
d 1.84–1.92 (m, 2H, CH2), 2.79 (t, J = 7.2 Hz, 2H, NCH2), 3.32
(t, J = 7.2 Hz, 2H, NCH2), 3.84 (s, 3H, OCH3), 5.09 (s, 2H, OCH2),
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Synthesis and Antibacterial Activity of New Diaryldiamines
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Scheme 3. Reagents and conditions: (i) 11a: Compound 18, K2CO3, DMSO, 80ꢀC, 48 h; yield 48%; 11b: Compound 22, K2CO3, DMSO, 80ꢀC, 48 h; yield
52%; (ii) 10% Pd-C, MeOH, rt, 1 h, yield quantitative; (iii) 3,4-Dichlorobenzaldehyde, MeONa, NaCNBH3, MeOH, 50ꢀC, 6 h; yield 11a: 48%; 11b: 52%.
Scheme 4. Reagents and condition: (i) NaN3, DMF, 24 h, 80ꢀC, yield quantitative; (ii) Allyl iodide, CsOHÁH2O, TBAI, 4Å MS, CH3CN, 48, rt, yield
80%; (iii) OsO4, NMO, acetone, H2O, 16 h, rt, yield 66%; (iv) 10% Pd-C, MeOH, rt, yield quantitative.
Scheme 5. Reagents and condition: (i) mCPBA, DCM, 3 h, rt, yield 80%; (ii) 28% aq. NH3, EtOH/H2O (1:1), 2 h, rt, yield 78%; (iii) (Boc)2O, DCM, 2 h/rt,
yield 90%; (iv) 10% Pd-C, EtOH, rt, yield quantitative.
6.11 (s, 1H, ArH), 6.90 (d, J = 8.58 Hz, 2H, ArH), 7.14–7.18 (m, 1H,
ArH), 7.38 (d, J = 8.58 Hz, 2H, ArH), 7.48–7.54 (m, 1H, ArH),
7.58–7.60 (m, 1H, ArH), 8.01–8.04 (m, 1H, ArH).
MeONa solution in methanol (1.0 mmol). The resulting reaction
mixture was stirred for 15 min at room temperature then
1-phenyl-3-aryl-1H-pyrazole-4-carbaldehyde 3’ (1.0 mmol) was
added, stirred at 50ꢀC for 1 h. A solution of NaCNBH3
(1.5 mmol) in MeOH (5 mL) was added dropwise and stirred
again for 6 h at 50ꢀC. Methanol was evaporated under reduced
pressure and crude product thus obtained was purified on silica
gel column using DCM/MeOH/NH3 sol (95:5:0.5) as eluent.
2-(3-((1,3-Diphenyl-1H-pyrazol-4-yl)methylamino)propylamino)
quinolin-4(1H)-one (4a). Solid; mp 210–212ꢀC; IR (KBr) n 3340
(NH), 1646 cmÀ1 (CO); MS (FAB) m/z 450 (MH+, 50), 329 (10), 233
(25); 1H NMR (CDCl3, 300 MHz), d 1.66 (m, 2H, CH2), 2.63
(t, J = 6.4 Hz, 2H, CH2), 3.16-3.18 (m, 2H, CH2), 3.72 (s, 2H, CH2),
5.58 (s, 1H, ArH), 6.79–6.80 (m, 1H, ArH), 7.06–7.20 (m, 3H, ArH),
7.24–7.38 (m, 4H, ArH), 7.63–7.72 (m, 5H, ArH), 7.88 (s, 1H,
Pyrazolyl), 8.16 (d, J = 1H, ArH); Anal. Calcd for C28H27N5O: C,
74.81; H, 6.05; N, 15.58. Found: C, 74.94; H, 6.20; N, 15.50.
2-(3-((1-Phenyl-3-p-tolyl-1H-pyrazol-4-yl)methylamino)
propylamino)quinolin-4(1H)-one (4b). Solid; mp 220–222ꢀC; IR
(KBr) n 3350 (NH), 1656 cmÀ1 (CO); MS (FAB) m/z 464
(MH+, 50), 329 (10), 233 (25); 1H NMR (CDCl3, 300 MHz),
d 1.64 (m, 2H, CH2), 2.30 (s, 3H, Me), 2.66 (t, J = 6.4 Hz, 2H,
CH2), 3.18–3.19 (m, 2H, CH2), 3.72 (s, 2H, NCH2), 5.56
(s, 1H, ArH), 6.79–6.80 (m, 1H, ArH), 7.06–7.20 (m, 3H, ArH),
7.24–7.38 (m, 3H, ArH), 7.63–7.72 (m, 5H, ArH), 7.88 (s, 1H,
Pyrazolyl), 8.16 (d, J = 8.10 Hz, 1H, ArH); Anal. Calcd for
1-Amino-3-[4-(4-methoxybenzyloxy) quinolin-2-yl-amino]
propan-2-ol (2b). A mixture of 1 (15.0 g, 50 mmol) and
2-hydroxy-1,3-diaminopropane (22.5 g, 250 mmol) was stirred in
DMSO (80 mL) at 80ꢀC in presence of potassium carbonate (8.3 g,
60 mmol) for 48 h. The reaction mixture was poured into distilled
water (50 mL) and extracted from ethyl acetate (25 mL Â 3),
dried over sodium sulfate, and evaporated. The solid obtained was
purified on silica gel column using CH2Cl2/MeOH/NH3 sol
(90:10:0.5) as eluent. White solid; mp 133–135ꢀC, IR (KBr) n 3336
1
cmÀ1 (OH); MS(FAB) m/z 354 (MH+, 30%); H NMR (CDCl3,
300 MHz) d 3.48–3.59 (m, 2H, NCH2), 3.64–3.69 (m, 2H, NCH2),
3.73–3.76 (m, 1H, CH), 3.88 (s, 3H, OCH3), 5.09 (s, 2H, OCH2),
6.37 (s, 1H, ArH), 6.94 (d, J = 8.70 Hz, 2H, ArH), 7.15–7.20
(m, 1H, ArH), 7.38 (d, J = 8.70 Hz, 2H, ArH), 7.48–7.53 (m, 1H,
ArH), 7.58–7.61 (m, 1H, ArH), 7.96–7.99 (m, 1H, ArH).
General procedure for the synthesis of 2-(3-((3-aryl-1-phenyl-
1H-pyrazol-4-yl)methylamino)propylamino)quinolin-4(1H)-one
(4a-f). A solution of N’-(4-(4-methoxybenzyloxy) quinolin-2-yl)
propane-1,3-diamine 2a (337 mg, 1 mmol) was stirred in 20%
TFA-DCM (10 mL) for 2 h at room temperature. TFA was
evaporated under reduced pressure and quinolin-4-one (3a) thus
obtained was dissolved in dry methanol (10 mL), acetic acid
(0.1 mL) was added at room temperature followed by 0.5 M
Journal of Heterocyclic Chemistry
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F. Samrin, A. Sharma, I. A. Khan, and S. Puri
Vol 49
Table 1
Antibacterial activity (MIC) of the synthesized compounds.
MIC (mg/mL)
Compounds
(4, 10, 13)
S. aureus
ATCC 29213
MRSA
15187
E. coli
ATCC 25922
P. aeruginosa
ATCC 27853
S. No
VRE
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
10a
10b
10c
10d
10e
32
32
Nil
Nil
32
Nil
128
Nil
64
64
32
Nil
Nil
32
Nil
256
Nil
128
128
Nil
Nil
128
16
32
32
Nil
Nil
32
Nil
256
Nil
128
128
Nil
Nil
128
16
>256
>256
Nil
Nil
>256
Nil
>256
Nil
>256
>256
Nil
>256
>256
Nil
Nil
>256
Nil
>256
Nil
>256
>256
Nil
9
10
11
12
13
14
15
16
17
18
19
20
21
64
Nil
Nil
128
16
Nil
Nil
>256
>256
>256
Nil
Nil
Nil
ND
ND
0.03
>256
>256
>256
Nil
Nil
Nil
ND
ND
0.06
64
64
64
Nil
Nil
Nil
ND
ND
0.25
Nil
Nil
Nil
ND
ND
16
Nil
Nil
Nil
ND
ND
32
10f
13a
13b
Ciprofloxacin
Nil, indicates insignificant activity; NT, indicates not determined; Ciprofloxacin, standard drug.
C29H29N5O: C, 75.14; H, 6.31; N, 15.11. Found: C, 75.20; H, 6.19;
N, 15.22.
Calcd for C29H26BrN5O: C, 63.64; H, 4.96; N, 13.25. Found: C,
63.50; H, 4.86; N, 13.38.
2-(3-((3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)
methylamino)propylamino)quinolin-4(1H)-one À(14c). Solid;
mp 234-236ꢀC; IR (KBr) n 3431 (NH), 1637 cm (CO); MS
(FAB) m/z 480 (MH+, 70), 460 (20), 329 (60); 1H NMR (CDCl3,
300 MHz), d 1.68 (m, 2H, CH2), 2.64 (t, J = 6.4 Hz, 2H, CH2),
3.18-3.19 (m, 2H, CH2), 3.68 (s, 2H, CH2), 3.70 (s, 3H, OCH3),
5.61 (s, 1H, ArH), 6.87–6.89 (m, 3H, ArH), 7.06–7.35 (m, 4H,
ArH), 7.61–7.67 (m, 4H, ArH), 7.84 (s, 1H, Pyrazolyl), 8.16
(d, J=8.1 Hz, 1H, ArH); Anal. Calcd for C29H29N5O2: C, 72.63;
H, 6.10; N, 14.60. Found: C, 72.52; H, 6.22; N, 14.38.
2-(3-((1-Phenyl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)methylamino)
propylamino) quinolin-4(1H)-one (4f). Solid; mp 205–206ꢀC; IR
(KBr) n 3432 (NH), 1638 cmÀ1 (CO); MS (FAB) m/z 456 (MH+,
1
50), 294 (10); H NMR (CDCl3, 300 MHz), d 1.68–1.72 (m, 2H,
CH2), 2.66 (t, J = 6.4 Hz, 2H, CH2), 3.19–3.20 (m, 2H, CH2),
3.70 (s, 2H, CH2), 5.62 (s, 1H, ArH), 6.96–6.98 (m, 2H, ArH),
7.07–7.19 (m, 3H, ArH), 7.25–7.37 (m, 3H, ArH), 7.58–7.61
(m, 2H, ArH), 7.81 (s, 1H, Pyrazolyl), 8.17 (d, J = 8.10 Hz, 1H,
ArH); Anal. Calcd for C26H25N5OS: C, 68.55; H, 5.53; N, 15.37.
Found: C, 68.68; H, 5.70; N, 15.48.
2-(3-((3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)
methylamino)propylamino)quinolin-4 (1H)-one (4dÀ).1 Solid;
General procedure for the synthesis of 2-(3-((1,3-diaryl-1H-
pyrazol-4-yl)methylamino)-2-hydroxypropylamino)quinolin-
4(1H)-one (4g-l). A mixture of 2b (1.0 mmol) was stirred with
20%TFA-DCM (10 mL) for 2 h at room temperature. TFA was
evaporated under reduced pressure and quinolin-4-one (3b) thus
obtained was dissolved in dry methanol (10 mL), acetic acid
(0.1 mL) was added at room temperature followed by 0.5 M
MeONa solution in methanol (1.0 mmol). The resulting reaction
mixture was stirred for 15 min at room temperature then
1-phenyl-3-aryl-1H-pyrazole-4-carbaldehyde 3’ (1.0 mmol) was
added, stirred at 50ꢀC for 1 h. A solution of NaCNBH3
(1.5 mmol) in MeOH (5 mL) was added dropwise and stirred
again for 6 h at 50ꢀC. Methanol was evaporated under reduced
pressure and crude product thus obtained was purified on silica
gel column using DCM/MeOH/NH3 sol (95:5:0.5) as eluent.
2-(3-((1,3-Diphenyl-1H-pyrazol-4-yl)methylamino)-2-
hydroxypropylamino)quinolin-4(1H)-one (4g). Solid; mp
203–204ꢀC; IR (KBr) n 3624 (OH), 3423 (NH), 1638 cmÀ1
(CO); MS (FAB) m/z 467 (M++2, 50), 233 (100); 1H NMR
(CDCl3, 300 MHz), d 2.48–2.49 (m, 2H, CH2), 3.08–3.09
mp 216–218ꢀC; IR (KBr) n 3436 (NH), 1639 cm
(CO);
MS (FAB) m/z 484 (MH+, 50), 463 (20), 329 (10); 1H NMR
(DMSO-d6, 300 MHz), d 1.75–1.79 (m, 2H, CH2), 2.71 (t, J = 6.4
Hz, 2H, CH2), 3.28-3.35 (m, 2H, CH2), 3.74 (s, 2H, CH2), 5.31
(brs, 1H, NH), 5.76 (s, 1H, ArH), 6.46 (brs, 1H, NH), 7.08–7.13
(m, 1H, ArH), 7.29–7.33 (m, 2H, ArH), 7.40–7.52 (m, 5H, ArH),
7.85–7.96 (m, 5H, ArH), 8.51 (s, 1H, ArH); Anal. Calcd for
C29H26ClN5O: C, 69.48; H, 5.41; N, 14.47. Found: C, 69.56; H,
5.58; N, 14.58.
2-(3-((3-(4-Bromophenyl)-1-phenyl-1H-pyrazol-4-yl)
methylamino) propylamino)quinolin-4(1H)-one (4e). Solid; mp
230–232ꢀC; IR (KBr) n 3432 (NH), 1638 cmÀ1 (CO); MS (FAB)
m/z 528 (MH+, 50), 460 (40), 329 (10); 1H NMR (DMSO-d6, 300
MHz), d 1.74–1.79 (m, 2H, CH2), 2.71 (t, J = 6.4 Hz, 2H, CH2),
3.27–3.35 (m, 2H, CH2), 3.74 (s, 2H, CH2), 5.28 (brs, 1H, NH),
5.76 (s, 1H, ArH), 6.43 (brs, 1H, NH), 7.08–7.13 (m, 1H, ArH),
7.28–7.33 (m, 2H, ArH), 7.40–7.52 (m, 3H, ArH), 7.62–7.64
(m, 2H, ArH), 7.85–7.92 (m, 5H, ArH), 8.51 (s, 1H, ArH); Anal.
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Synthesis and Antibacterial Activity of New Diaryldiamines
1395
(m, 2H, CH2), 3.60–3.75 (m, 3H, CH2), 5.62 (s, 1H, ArH), 6.92–6.94
(m, 2H, ArH), 7.12–7.32 (m, 7H, ArH), 7.56–7.83 (m, 4H, ArH),
7.83 (s, 1H, Pyrazolyl), 8.02 (d, J = 7.50 Hz, 1H, ArH); Anal.
Calcd for C28H27N5O2: C, 72.24; H, 5.85; N, 15.04. Found: C,
72.36; H, 5.97; N, 15.18.
thrice and dried in the air. White solid; mp >250ꢀC; MS (EI)
m/z 162 (M+, 86%) [13].
2,4-Dichloroquinazoline (7). A solution of quinazolin-2,
4-dione 6 (2 g) in phosphorousoxychloride (POCl3, 6 mL) was
refluxed in presence of N,N-diethylaniline (0.6 mL) for 5 h. The
reaction mixture was allowed to cool to room temperature and
poured over crushed ice with vigrourous stirring. Dark brown
solid precipitate obtained was filtered, washed with distilled water
and finally purified on silica gel column chromatography using
hexane/ethyl acetate (40:1) as eluent. White solid; mp 116–117ꢀC;
[Lit. [13] mp 116–117ꢀC]; MS (EI) m/z 199 (M+, 78.0).
2-Chloroquinazolin-4(1H)-one (8). A suspension of 7 (1.0 mmol)
was stirred in 4% aq. sodium hydroxide solution (3 mL) for
3 h. Reaction mixture was diluted with water (6 mL) and
filtered to remove unreacted 2,4-dichloroquinazoline. The
filtrate was neutralized with dilute acetic acid, white
precipitate obtained was filtered and washed with water.
White solid; mp 220–221ꢀC [Lit. [13] mp 220–221ꢀC];
MS (EI) m/z 180 (M+, 51.0).
2-(3-Aminopropylamino)quinazolin-4(1H)-one (9). A mixture
of 8 (0.1 mol) and 1,3-diaminopropane (8 mL) was heated to
70ꢀC for 48 h. At the end of the reaction 1,3-diaminopropane
was evaporated under reduced pressure and washed with
dichloromethane (10 mL Â 2) to reveal desired compound (9).
White solid; mp 145–147ꢀC (decomposed); MS (FAB) m/z 219
(MH+, 100%); 1H NMR (CD3OD, 300 MHz), d 1.72–1.75
(m, 2H, CH2), 2.89–2.91 (m, 2H, CH2), 3.53–3.56 (m, 2H, CH2),
7.16–7.20 (m, 1H, ArH), 7.30–7.32 (m, 1H, ArH), 7.57–7.61
(m, 1H, ArH), 8.00–8.01 (m, 1H, ArH).
2-(2-Hydroxy-3-((1-phenyl-3-p-tolyl-1H-pyrazol-4-yl)
methylamino) propylamino)quinolin-4(1H)-one (4h). Solid; mp
208–210ꢀC; IR (KBr) n 3622 (OH), 3434 (NH), 1638 cmÀ1 (CO);
1
MS (FAB) m/z 481 (M++2, 50), 263 (40); H NMR (CDCl3, 300
MHz), d 2.32 (s, 3H, Me), 2.48-2.49 (m, 2H, CH2), 3.08-3.09
(m, 2H, CH2), 3.60–3.75 (m, 3H, CH2), 5.62 (s, 1H, ArH),
6.92–6.94 (m, 2H, ArH), 7.12–7.32 (m, 6H, ArH), 7.56–7.83
(m, 4H, ArH), 7.83 (s, 1H, Pyrazolyl), 8.02 (d, J = 8.10 Hz, 1H,
ArH); Anal. Calcd for C29H29N5O2: C, 72.63; H, 6.10; N, 14.60.
Found: C, 72.78; H, 6.24; N, 14.74.
2-(2-Hydroxy-3-((3-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-
4-yl) methylamino) propylamino)quinolin-4(1H)-one (4i). Solid;
mp 205–206ꢀC; IR (KBr) n 3622 (OH), 3434 (NH), 1638 cmÀ1
(CO); MS (FAB) m/z 496 (MH+, 50), 263 (40); 1H NMR (DMSO-
d6, 300 MHz), d 2.64-2.75 (m, 2H, CH2), 3.08–3.09 (m, 2H, CH2),
3.72–3.83 (m, 6H, CH2 and OMe), 5.38 (brs, 1H, NH), 5.76 (s, 1H,
ArH), 6.36 (brs, 1H, NH), 6.98–7.01 (m, 2H, ArH), 7.08–7.13
(m, 1H, ArH), 7.23–7.30 (m, 2H, ArH), 7.40–7.51 (m, 3H, ArH),
7.80–7.92 (m, 5H, ArH and Pyrazolyl), 8.47 (s, 1H, ArH); Anal.
Calcd for C29H29N5O3: C, 70.28; H, 5.90; N, 14.13. Found: C,
70.34; H, 5.82; N, 14.24.
2-(3-((3-(4-Fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)
methylamino)-2-hydroxypropylamino)quinolin-4(1H)-one
(4j). Solid; mp 236–237ꢀC; IR (KBr) n 3622 (OH), 3423 (NH),
1638 cmÀ1 (CO); MS (FAB) m/z 484(MH+, 50), 251 (80); 1H
NMR (CDCl3, 300 MHz), d 2.48–2.50 (m, 2H, CH2), 3.08–3.09
(m, 2H, CH2), 3.49–3.60 (m, 2H, CH2), 3.78–3.80 (m, 1H, CH),
5.64 (s, 1H, ArH), 6.87–6.98 (m, 4H, ArH), 7.07–7.12 (m, 3H,
ArH), 7.21–7.25 (m, 2H, ArH), 7.52–7.61 (m, 3H, ArH), 7.80
(s, 1H, Pyrazolyl), 8.01 (d, J = 7.8 Hz, 1H, ArH); Anal. Calcd for
C28H26FN5O2: C, 69.55; H, 5.42; N, 14.48. Found: C, 69.66; H,
5.56; N, 14.42.
General procedure for the synthesis of 2-(3-(substituted
benzylamino)propylamino)quinazolin-4(1H)-one (10a-f).
A
solution of 9 (1.0 mmol) in dry methanol (10 mL), acetic acid
(0.1 mL) was added at room temperature followed by 0.5 M
MeONa solution in methanol (1.0 mmol). The resulting reaction
mixture was stirred for 15 min at room temperature then suitable
aldehyde (1.0 mmol) was added, stirred at 50ꢀC for 1 h. A solution
of NaCNBH3 (1.5 mmol) in MeOH (5 mL) was added dropwise
and stirred again for 6 h at 50ꢀC. Methanol was evaporated under
reduced pressure and crude product thus obtained was purified on
silica gel column using DCM/MeOH/NH3 sol (95:5:0.5) as eluent.
2-(3-(4-Chlorobenzylamino)propylamino)quinazolin-4(1HÀ)-1
one (10a). Solid; mp 84–85ꢀC; IR (KBr) n 3464 (NH), 1641 cm
(CO); MS (FAB) m/z 343 (MH+, 100), 202 (10); 1H NMR
(CD3OD, 300 MHz), d 1.66–1.70 (m, 2H, CH2), 2.48–2.50
(m, 2H, CH2), 3.31–3.33 (m, 2H, CH, CH2), 3.57 (s, 2H, CH2),
7.08–7.12 (m, 6H, ArH), 7.39–7.41 (m, 1H, ArH), 7.82–7.84
(m, 1H, ArH); Anal. Calcd for C18H19ClN4O: C, 63.06; H, 5.59;
N, 16.34. Found: C, 63.14; H, 5.66; N, 16.48.
2-(3-((3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)
methylamino)-2-hydroxypropylamino)quinolin-4(1H)-one
(4k). Solid; mp 251–252ꢀC; IR (KBr) n 3622 (OH), 3387 (NH),
1
1638 cmÀ1 (CO); MS (FAB) m/z 500 (MH+, 50), 267 (60); H
NMR (CD3OD, 300 MHz), d 2.71–2.83 (m, 2H, CH2), 3.29–3.33
(m, 2H, CH2), 3.91–3.95 (m, 3H, CH, CH2), 5.56 (s, 1H, ArH),
7.21–7.33 (m, 3H, ArH), 7.41–7.52 (m, 5H, ArH), 7.74–7.78
(m, 4H, ArH), 8.08–8.09 (m, 1H, Pyrazolyl), 8.01 (s, 1H, ArH);
Anal. Calcd for C28H26ClN5O2: C, 67.26; H, 5.24; N, 14.01.
Found: C, 67.36; H, 5.32; N, 14.14.
2-(2-Hydroxy-3-((1-phenyl-3-(thiophen-2-yl-1H-pyrazol-4-yl)
methylamino) propylamino)quinolin-4(1H)-one (4l). Solid; mp
241–242ꢀC; IR (KBr) n 3622 (OH), 3421 (NH), 1644 cmÀ1
(CO); MS (FAB) m/z 472 (MH+, 50), 239 (10); 1H NMR (CDCl3,
300 MHz), d 2.61–2.64 (m, 2H, CH2), 3.09–3.12 (m, 2H, CH2),
3.75–3.89 (m, 3H, CH, CH2), 5.61 (s, 1H, ArH), 6.92–6.98
(m, 3H, ArH), 7.11–7.13 (m, 3H, ArH), 7.22–7.26 (m, 4H, ArH),
7.52–7.55 (m, 2H, ArH and Pyrazolyl), 7.90–7.92 (m, 1H, ArH);
Anal. Calcd for C26H25N5O2S: C, 66.22; H, 5.34; N, 14.85.
Found: C, 66.36; H, 5.32; N, 14.74.
2-(3-(3,4-Dichlorobenzylamino)propylamino)quinazolin-4
(1H)-one (10b). Solid; mp 105–107ꢀC; IR (KBr) n 3470 (NH),
1
1690 cmÀ1 (CO); MS (FAB) m/z 377 (MH+, 80), 202 (10); H
NMR (CD3OD, 300 MHz), d 1.82–1.87 (m, 2H, CH2), 2.64–2.67
(m, 2H, CH2), 3.48–3.51 (m, 2H, CH, CH2), 3.71 (s, 2H, CH2),
7.14–7.24 (m, 3H, ArH), 7.34–7.36 (m, 1H, ArH), 7.47–7.48
(m, 1H, ArH), 7.54–7.57 (m, 1H, ArH), 7.97–7.98 (m, 1H, ArH);
Anal. Calcd for C18H18Cl2N4O: C, 57.30; H, 4.81; N, 14.85.
Found: C, 57.38; H, 4.92; N, 14.98.
Quinazolin-2,4-dione (6). Anthranilic acid 5 (13.7 g, 0.1 mol)
was added in portions to a molten urea (9.0 g, 0.15 mol) at 190ꢀC
for 30 min. The temperature of the raction mixture was
maintained for 1 h, cooled to room temperature and diluted with
water. The solid settled was filtered, washed with water (20 mL)
2-(3-(4-Bromobenzylamino) propylamino) quinazolin-4(1H)-
one (10c). Solid; mp 88–89ꢀC; IR (KBr) n 3472 (NH), 1637 cmÀ1
(CO); MS (FAB) m/z 387 (MH+, 100), 202 (10); 1H NMR
(CD3OD, 300 MHz), d 1.65–1.70 (m, 2H, CH2), 2.47–2.52
(m, 2H, CH2), 3.31–3.36 (m, 2H, CH, CH2), 3.57 (s, 2H, CH2),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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F. Samrin, A. Sharma, I. A. Khan, and S. Puri
Vol 49
6.99–7.08 (m, 4H, ArH), 7.23–7.25 (m, 2H, ArH), 7.39–7.41
(m, 1H, ArH), 7.82–7.84 (m, 1H, ArH); Anal. Calcd for
C18H19BrN4O: C, 55.82; H, 4.95; N, 14.47. Found: C, 55.70; H,
4.88; N, 14.56.
methanol (50 mL) was stirred with 10%Pd-C (100 mg) under H2
gas balloon for 1h at room temperature. The reaction mixture
was passed through celite pad. Filtrate was evaporated under
vacuum to get compound 12a in good purity. White solid; IR
(KBr) n 1710 (CO), 3660 cmÀ1 (OH); MS(FAB) m/z 308
(MH+, 100%); 1H NMR (CD3OD, 300 MHz) d 3.48–3.59
(m, 2H, NCH2), 3.68–3.70 (m, 2H, NCH2), 3.74–3.75 (m, 1H,
CH), 3.80–3.82 (m, 4H, CH2), 3.95–3.96 (m, 1H, CH), 5.68
(s, 1H, ArH), 7.23–7.30 (m, 2H, ArH), 7.40 (d, J = 8.70 Hz, 1H,
ArH), 8.06 (d, J = 8.10 Hz, 1H, ArH).
2-(3-(Pyridin-4-ylmethylamino) propylamino)quinazolin-4
(1H)-one (10d). Solid; mp 110–112ꢀC; IR (KBr) n 3474 (NH),
1
1640 cmÀ1 (CO); MS (FAB) m/z 310 (MH+, 60), 202 (10); H
NMR (CD3OD, 300 MHz), d 1.88–1.92 (m, 2H, CH2), 2.69–2.74
(m, 2H, CH2), 3.52–3.57 (m, 2H, CH2), 3.84 (s, 2H, CH2),
7.18–7.29 (m, 2H, ArH), 7.41–7.43 (m, 2H, ArH), 7.57–7.63
(m, 1H, ArH), 8.01–8.03 (m, 1H, ArH), 8.42–8.44 (m, 2H, ArH);
Anal. Calcd for C17H19N5O: C, 66.00; H, 6.19; N, 22.64. Found:
C, 66.14; H, 6.28; N, 22.56.
tert-Butyl 3-(1-amino-3-(4-oxo-1,4-dihydroquinolin-2-ylamino)
propan-2-yloxy)-2-hydroxypropylcarbamate (12b). Compound
12b was synthesized from compound 11b according to the
procedure for preparation of compound 12a. White solid, IR
(KBr) n 1710 (CO), 3430 (NH), 3650 cmÀ1 (OH); MS(FAB) m/z
2-(3-(Thiophen-2-ylmethylamino)propylamino)quinazolin-
4(1H)-one (10e). Solid; mp 114–116ꢀC; IR (KBr) n 3470 (NH),
1
1
1642 cmÀ1 (CO); MS (FAB) m/z 315 (MH+, 100), 202 (10); H
407 (MH+, 100%); H NMR (CDCl3, 300 MHz) d 1.41 (s, 9H,
NMR (CD3OD, 300 MHz), d 1.85–1.89 (m, 2H, CH2), 2.71–2.76
(m, 2H, CH2), 3.50–3.52 (m, 2H, CH2), 3.99 (s, 2H, CH2),
6.92–6.99 (m, 2H, ArH), 7.18–7.29 (m, 3H, ArH), 7.57–7.62
(m, 1H, ArH), 8.01–8.03 (m, 1H, ArH); Anal. Calcd for
C16H18N4OS: C, 61.12; H, 5.77; N, 17.82. Found: C, 61.18; H,
5.88; N, 17.96.
Boc), 3.48–3.59 (m, 2H, NCH2), 3.64–3.65 (m, 2H, NCH2),
3.68–3.96 (m, 2H, CH2), 3.73–3.76 (m, 1H, CH), 3.82–3.84
(m, 2H, CH2), 3.92–3.93 (m, 1H, CH), 5.68 (s, 1H, ArH),
7.23–7.30 (m, 2H, ArH), 7.40 (d, J = 8.70 Hz, 1H, ArH), 8.06
(d, J = 8.10 Hz, 1H, ArH).
2-(3-(3,4-Dichlorobenzylamino)-2-(2,3-dihydroxypropoxy)
propylamino)quinolin-4(1H)-one (13a). To a stirred solution of
12a (123 mg, 0.40 mmol) in methanol (5 mL) was added 0.5 M
methanolic solution of MeONa (1 mL, 0.43 mmol). Additional
amount of 0.5 M MeONa solution was added to maintain pH 12
of the reaction mixture and stirred for 10 min at room
temperature. 3,4-Dichlorobenzaldehyde (70 mg, 0.40 mmol) was
added and resultant reaction mixture was stirred at 50ꢀC for 1 h.
To this NaCNBH3 (38 mg, 0.60 mmol) in methanol (2 mL) was
added dropwise and stirring continued for additional 6 h. Solvent
was evaporated under reduced pressure and residue obtained was
purified on silica gel column chromatography using DCM/MeOH/
NH3 solution (95:5:1) as eluent. White solid; mp 152–154ꢀC; IR
(KBr) n 1710 (CO), 3660 cmÀ1 (OH), MS (FAB) 467 (MH+);
1H NMR (CD3OD, 300 MHz) d 3.48–3.59 (m, 2H, NCH2),
3.68–3.70 (m, 2H, NCH2), 3.74–3.75 (m, 3H, CH and CH2),
3.80–3.82 (m, 4H, CH2), 3.95–3.96 (m, 1H, CH), 5.67 (s, 1H, ArH),
7.24–7.28 (m, 1H, ArH), 7.34–7.39 (m, 2H, ArH), 7.52–7.56
(m, 2H, ArH), 7.63–7.65 (m, 1H, ArH), 8.06 (d, J = 8.10 Hz, 1H,
ArH). Anal. Calcd for C22H25 Cl2N3O4: C, 56.66; H, 5.40; N, 9.01.
Found: C, 56.78; H, 5.54; N, 9.18.
tert-Butyl 3-(1-(3,4-Dichlorobenzylamino)-3-(4-oxo-
1,4-dihydroquinolin-2-ylamino)propan-2-yloxy)-2-
hydroxypropylcarbamate (13b). This compound was synthesized
from the reaction of compound 12b and 3,4-dichlorobenzaldehyde
according to the procedure described for compound 13a. White
solid, IR (KBr) n 1710 (CO), 3430 (NH), 3650 cmÀ1 (OH); MS
(FAB) m/z 566 (MH+, 100%); 1H NMR (CDCl3, 300 MHz) d
1.41 (s, 9H, Boc), 3.48–3.59 (m, 2H, NCH2), 3.64–3.65 (m, 2H,
NCH2), 3.68–3.96 (m, 2H, CH2), 3.73–3.76 (m, 3H, CH and
CH2), 3.82–3.84 (m, 2H, CH2), 3.92–3.93 (m, 1H, CH), 5.67
(s, 1H, ArH), 7.24–7.28 (m, 1H, ArH), 7.34–7.39 (m, 2H, ArH),
7.52–7.56 (m, 2H, ArH), 7.63–7.65 (m, 1H, ArH), 8.06
(d, J=8.10 Hz, 1H, ArH). Anal. Calcd for C27H34 Cl2N4O5: C,
57.35; H, 6.06; N, 9.91. Found: C, 57.48; H, 6.20; N, 9.84.
1,3-Diazidopropan-2-ol (15). A mixture of 14 (10.85 g,
50.0 mmol) and sodium azide (9.75 g, 150.0 mmol) in DMF
was heated at 80ꢀC for 24 h. The reaction mixture was allowed
to cool to room temperature, diluted with water and extracted
with ethyl acetate (25 mL Â 3). Organic layer was collected,
washed with excess of water and dried under vacuum. The
2-(3-(Naphthalen-1-ylmethylamino)propylamino)quinazolin-
4(1H)-one (10f). Solid; mp 145–146ꢀC; IR (KBr) n 3480 (NH),
1
1644 cmÀ1 (CO); MS (FAB) m/z 315 (MH+, 100), 202 (10); H
NMR (CDCl3, 300 MHz), d 1.88–1.90 (m, 2H, CH2), 2.82–2.84
(m, 2H, CH2), 3.24–3.27 (m, 2H, CH2), 3.78 (s, 2H, CH2),
7.40–7.58 (m, 6H, ArH), 7.86–7.89 (m, 3H, ArH), 7.98–7.99
(m, 1H, ArH), 8.56–8.58 (m, 1H, ArH); Anal. Calcd for
C22H22N4O: C, 73.72; H, 6.19; N, 15.63. Found: C, 73.88; H,
6.10; N, 15.56.
3-(1-Amino-3-(4-(4-methoxybenzyloxy)quinolin-2-ylamino)
propan-yloxy)propane-1,2-diol (11a). A mixture of 1 (1.50 g,
5.0 mmol) and compound 18 (4.10 g, 25.0 mmol) was stirred in
DMSO (30 mL) at 80ꢀC in presence of potassium carbonate
(0.83 g, 6.0 mmol) for 48 h. The reaction mixture was poured
into distilled water (50 mL) and extracted from ethyl acetate
(25 mL Â 3), dried over sodium sulfate, and evaporated. The
solid obtained was purified on silica gel column using CH2Cl2/
MeOH/ NH3 sol (90:10:0.5) as eluent. White solid; IR (KBr) n
3660 cmÀ1 (OH); MS(FAB) m/z 428 (MH+, 100%); 1H NMR
(CDCl3, 300 MHz) d 3.48–3.59 (m, 2H, NCH2), 3.64–3.69
(m, 2H, NCH2), 3.73–3.76 (m, 1H, CH), 3.80–3.82 (m, 4H, CH2),
3.88 (s, 3H, OCH3), 3.95–3.96 (m, 1H, CH), 5.10 (s, 2H, OCH2),
6.40 (s, 1H, ArH), 6.96 (d, J = 8.70 Hz, 2H, ArH), 7.15–7.20
(m, 1H, ArH), 7.40 (d, J = 8.70 Hz, 2H, ArH), 7.48–7.53 (m, 1H,
ArH), 7.58–7.61 (m, 1H, ArH), 7.96–7.99 (m, 1H, ArH).
tert-Butyl 3-(1-Amino-3-(4-(4-methoxybenzyloxy)quinolin-
2-ylamino)propan-2-yloxy)-2-hydroxypropylcarbamate
(11b). This compound was synthesized from compound 1 and
compound 22 by following the procedure of preparation of
compound 11a. White solid, IR (KBr) n 3420 (NH), 3640 cmÀ1
1
(OH); MS(FAB) m/z 527 (MH+, 100%); H NMR (CDCl3, 300
MHz) d 1.41 (s, 9H, Boc), 3.48–3.59 (m, 2H, NCH2), 3.64–3.65
(m, 2H, NCH2), 3.68–3.96 (m, 2H, CH2), 3.73–3.76 (m, 1H, CH),
3.82–3.84 (m, 2H, CH2), 3.90 (s, 3H, OCH3), 3.92–3.93 (m, 1H,
CH), 5.10 (s, 2H, OCH2), 6.50 (s, 1H, ArH), 6.94 (d, J = 8.70 Hz,
2H, ArH), 7.16–7.18 (m, 1H, ArH), 7.42 (d, J = 8.70 Hz,
2H, ArH), 7.50–7.51 (m, 1H, ArH), 7.59–7.61 (m, 1H, ArH),
7.94–7.96 (m, 1H, ArH).
2-(3-Amino-2-(2,3-dihydroxypropoxy)propylamino)quinolin-
4(1H)-one (12a). A solution of compound 11a (500 mg) in
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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1397
residue obtained was purified by silica gel column using Hexane:
EtOAc (9:1). Colorless oil; MS (FAB) 143 (MH+); 1H NMR
(CDCl3, 300 MHz) d 3.36–3.37 (m, 4H, CH), 3.66–3.68
(m, 1H, CH).
3.36–3.38 (m, 4H, CH2), 3.60–3.62 (m, 1H, CH), 3.68–3.69
(m, 2H, CH2), 3.72–3.74 (m, 1H, CH).
tert-Butyl 3-(1,3-diazidopropan-2-yloxy)-2-hydroxypropylcar-
bamate (21). A solution of compound 20 (2.0 g, 9.26 mmol) in
DCM (15 mL) was added (Boc)2O (2.22 g, 10.24 mmol) and
stirred at room temperature for 1 h. DCM was evaporated and
residue obtained was purified on silica gel column using ethyl
acetate: hexane (1:9) as eluent. Colorless oil; MS (FAB)
3-(2-Azido-1-azidomethylethoxy)-propene (16). A mixture of
15 (5.0 g, 35.2 mmol), 4Å molecular sieves (20 g) and
CsOHÁH2O (11.8 g, 70.4 mmol) in acetonitrile (30 mL) was
stirred at room temperature for 20 min under nitrogen atmosphere.
n-tetrabutylammonium iodide (12.98 g, 35.2 mmol) and allyl
iodide (9.58 mL, 105.6 mmol) were added sequentially and
resultant mixture stirred for 48 h at room temperature. Solid
insoluble was filtered and solvent evaporated under reduced
pressure. The crude product was purified on silica gel column
using hexane: EtOAc (19:1) as eluent. Colorless oil; MS (FAB)
1
316 (MH+); H NMR (CD3Cl3, 300 MHz) d 1.41 (s, 9H, Boc),
3.30–3.32 (m, 2H, CH2), 3.35–3.36 (m, 4H, CH2), 3.60–3.61
(m, 1H, CH), 3.66–3.68 (m, 2H, CH2), 3.72–3.74 (m, 1H, CH).
tert-Butyl 3-(1,3-diaminopropan-2-yloxy)-2-hydroxypropylcar-
bamate (22). A mixture compound 21 (2.0 g) and 10% Pd(OH)2
(100 mg), under hydrogen atmosphere in methanol at room
temperature for 20 h. The reaction mixture was filtered through celite
powder and evaporated under vacuum. The product obtained was
directly used for next stage without purification.
1
183 (MH+); H NMR (CDCl3, 300 MHz) d 3.37–3.39 (m, 4H,
CH), 3.68–3.69 (m, 1H, CH), 4.13–4.15 (m, 2H, allyl), 5.21–5.36
(m, 2H, allyl), 5.87–6.00 (m, 1H, allyl).
3-(1,3-Diazidopropan-2-yloxy)propane-1,2-diol (17).
A
mixture of compound 16 (1.82 g, 10.0 mmol) and N-methylmorpholine
N-oxide (NMO) (1.755 g, 15.0 mmol) in acetone/water (10:1;
22 mL) was added osmium tetraoxide (2.5% wt solution in
tert-butanol; 100 mL, 0.10 mmol) and allowed to stir at room
temperature for 16 h. The solvent of the reaction mixture was
evaporated and extracted with ethyl acetate (15 mL Â 2). The
ethyl acetate layers were separated, dried (Na2SO4), evaporated
under reduced pressure and crude obtained was purified by silica
gel chromatography using hexane: ethyl acetate (1:1) as eluent to
get compound 17. Colorless oil; MS (FAB) 217 (MH+); 1H NMR
(CD3Cl3, 300 MHz) d 3.36–3.37 (m, 4H, CH2), 3.66–3.68
(m, 1H, CH), 3.80–3.82 (m, 4H, CH2), 3.95–4.01 (m, 1H, CH).
REFERENCES AND NOTES
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M. J.; Elder, J. S.; Forrest, A. K.; Fosberry, A. P.; Gentry, D. R.; Hibbs,
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3-(1,3-Diaminopropan-2-yloxy)propane-1,2-diol (18).
A
mixture compound 17 (1.0 g) and 10% Pd(OH)2 (50 mg), under
hydrogen atmosphere in methanol at room temperature for 20 h.
The reaction mixture was filtered through celite powder and
evaporated under vacuum. The product obtained was directly
used for next stage without purification.
2-((1,3-Diazidopropan-2-yloxy)methyl)oxirane (19). A mixture
of compound 16 (1.82 g, 10.0 mmol) and 3-chloroperoxybenzoic
acid (2.5 g, 15.0 mmol) in DCM (20 mL) was stirred at room
temperature for 1.5 h. DCM was evaporated and residue obtained
was purified on silica gel column using ethyl acetate: hexane (1:4)
as eluent. Colorless oil; MS (FAB) 199 (MH+); 1H NMR
(CD3Cl3, 300 MHz) d 3.38–3.39 (m, 4H, CH2), 3.68–3.69
(m, 1H, CH), 3.80–3.82 (m, 2H, CH2), 4.10–4.12 (m, 1H, CH),
4.20–4.22 (m, 2H, CH2).
1-Amino-3-(1,3-diazidopropan-2-yloxy)propan-2-ol (20). A
solution of compound 19 (1.99 g, 10.0 mmol) in ethanol (15 mL)
was added 28% aq. solution NH3 (1.2 mL, 20.0 mmol) dropwise
and stirred at room temperature for 3 h. ethanol was evaporated
and residue obtained was purified on silica gel column using ethyl
acetate: hexane (1:1) as eluent. Colorless oil; MS (FAB) 216
(MH+); 1H NMR (CD3Cl3, 300 MHz) d 3.32–3.34 (m, 2H, CH2),
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet