Supporting Information
Concise Synthesis of Substituted Meridianins
T. A. Jenifer Vijay, Kebbahalli N. Nandeesh, Nagarakere C. Sandhya, G. P. Suresha, Kanchugarakoppal. S. Rangappa,* and Kempegowda
Mantelingu,*
a
Department of Studies in Chemistry, Manasagangothri, University of Mysore, Mysore-570006, INDIA
 Corresponding author. Tel.: +91 821 2412191/2419661; fax: +91 821 2412191.
E-mail address: kmantelingu@yahoo.com (K. Mantelingu).
Contents
Experimental methods
S2
Spectral data
S3
1
S6
H NMR and 13CNMR and LCMS spectra of synthesized compounds
Experimental
Materials and methods
All reagents and starting materials were purchased from known commercial sources and used without further purification, unless
otherwise noted. All analytical thin layer chromatography was performed with E. Merck silica gel 60F254 aluminum sheets and was
visualized with UV light. The following mobile phases were employed for TLC: hexane and ethyl acetate in different ratios. Melting
points were determined in open capillaries and are uncorrected. Infrared (IR) spectra were recorded on FT-IR spectrometer (KBr) and
wavelengths (λ) are reported in cm-1. 1H NMR and 13C NMR spectra were collected at NMR Facility, IOE, University of Mysore,
Manasagangotri, Mysore. Chemical shifts are reported in ppm relative to residual solvent (CDCl3 and DMSO-d6). Unless otherwise
noted, spectra were collected at room temperature. Mass and purity were recorded on a LC–MSD-Trap-XCT. The C, H, and N
analyses were performed from micro analytical laboratory.
Synthesis
Preparation of N-benzyl-3-acetylindole.
A mixture of 3-acetylindole (2.5 g, 15.72 mmol), potassium hydroxide (1.25g, 22.27 mmol) in dry DMF (10 mL) was stirred until
soulibilization of KOH. Next, benzyl bromide (1.4 mL, 11.77mmol) was added and stirred at room temperature until 3-acetylindole
disappeared (monitored by TLC). After completion of reaction the mixture was poured into water and extracted to ethyl acetate, was
dried over sodium sulfate. Solvent was removed and half-white solid was recrystallized with diethyl ether.
Preparation of 1-(1-benzyl-1H-indol-3-yl)-3-(het)aryl-3-thioxopropan-1-one derivatives 4(a-d).
To a 60% suspension of NaH in mineral oil (0.06g, 2.5 mmol) in DMF (2 mL) at 0 °C N-benzyl-3-acetylindole (0.249g, 1.0 mmol)
was added followed by stirring for 10_15 min at room temperature. A solution of dithioester (1.0 mmol) in DMF (2 mL) was added
over a period of 10 min at 0 °C followed by stirring at room temperature for 6-7 h. The completion of the reaction was monitored by
TLC. The mixture was poured into water and extracted with ethyl acetate (2 × 25 mL). The combined organic layer was washed with
brine (25 mL) and dried over anhydrous sodium sulphate. The solvent was removed under reduced pressure and the crude product was
passed through a small plug of silica using hexane/ethyl acetate (9:1) to afford 1-(1-benzyl-1H-indol-3-yl)-3-(het)aryl-3-thioxopropan1-one derivatives 4(a-d).
Preparation of meridianin analogs 5(a-d).
Guanidine hydrochloride (0.142 g, 1.5 mmol) was added to a stirred suspension of K2CO3 (0.346 g, 2.5 mmol) in EtOH (95%; 10
mL), and then a solution of 1-(1-benzyl-1H-indol-3-yl)-3-(het)aryl-3-thioxopropan-1-one (1.0 mmol) in ethanol (2 mL) was added.
The reaction mixture was heated at reflux with stirring for 5–6 h (monitored by TLC). The mixture was then filtered over Celite® S
and the filtrate was concentrated to dryness under reduced pressure, and the residue was extracted with ethyl acetate (2 × 25 mL). The
organic phase was washed with water (2× 25 mL) and brine (25 mL), dried (Na2SO4), and concentrated under reduced pressure to give
crude products which were purified by column chromatography on silica gel using hexane/ethyl acetate (7:3) to afford meridianins
analogs 5(a-d).
Characterization Data
4-(1-benzyl-1H-indol-3-yl)-6-phenylpyrimidin-2-amine (5a): Following the general procedure, compound 5a was obtained from
the reaction between
1-(1-benzyl-1H-indol-3-yl)-3-phenyl-3-thioxopropan-1-one (4a) and
guanidine
1
hydrochloride as a cream color solid in 71 % yield; mp 164–166 °C; H NMR (400 MHz, DMSO-d6): δ 8.42 (d,
J = 8.0 Hz, 1H, aromatic CH), 8.04 (d, J = 7.4 Hz, 2H, aromatic CH), 7.93 (s, 1H, 2-H of indolyl), 7.51–7.47 (m,
3H, aromatic CH), 7.43 (s, 1H, N-heteroaryl CH), 7.36–7.19 (m, 6H, aromatic CH), 7.18 (d, J = 6.4 Hz, 2H,
aromatic CH), 5.39 (s, 2H, NH2), 5.19 (s, 2H, N-CH2); 13C NMR (100 MHz, DMSO-d6): δ 164.0, 163.2, 158.3,
137.9, 133.3, 131.1, 129.1, 127.6, 127.4, 126.5, 124.0, 123.0, 121.6, 113.7, 111.0, 106.6 (CH) , 50.8 (CH2) ; IR
(KBr): 3332 , 3089, 2955, 2861, 1582, 1505, 1049, 865, 753 cm-1; MS (ESI + ion): m/z = 377.2 (M +). Anal. Cacld for C25H20N4: C,
79.76; H, 5.35; N, 14.88. Found: C, 79.74; H, 5.34; N, 14.87.
4-(1-benzyl-1H-indol-3-yl)-6-(4-methoxyphenyl)pyrimidin-2-amine (5b): Following the general procedure, compound 5b was
obtained from the reaction between 1-(1-benzyl-1H-indol-3-yl)-3-(4-methoxyphenyl)-3-thioxopropan-1-one
(4b) and guanidine hydrochloride as a half-white solid in 76 % yield; mp 195-196 °C; 1H NMR (400 MHz,
DMSO-d6): δ 8.43 (d, J = 6.8 Hz, 1H, aromatic CH), 8.05 (d, J = 6.8 Hz, 2H, aromatic CH), 7.94 (s, 1H, 2-H of indolyl), 7.51–7.48
(m, 3H, aromatic CH), 7.44 (s, 1H, N-heteroaryl CH), 7.36–7.28 (m, 7H, aromatic CH), 7.19 (d, J = 8.0 Hz, 2H, aromatic CH), 5.40 (s,
2H, NH2), 5.20 (s, 2H, N-CH2), 3.84 (s, 3H, OCH3); 13C NMR (100 MHz, DMSO-d6): δ 164.1, 164.0, 163.2, 158.3, 136.9, 131.1,
130.1, 128.3, 127.5, 127.4, 126.1, 123.0, 122.0, 120.6, 113.8, 110.0, 100.0 (CH), 55.2 (CH2) , 50.7 (OCH3); IR (KBr): 3330, 3150,
2595, 2761, 1573, 1604, 1300, 1150, 765, 642 cm-1; MS (ESI + ion): m/z = 407.7 (M +). Anal. Cacld for C24H17NOS: C, 76.83; H,
5.46; N, 13.78. Found: C, 76.81; H, 5.45; N, 13.79.
4-(1-benzyl-1H-indol-3-yl)-6-(thiophen-2-yl)pyrimidin-2-amine (5c): Following the general procedure, compound 5c was obtained
from the reaction between 1-(1-benzyl-1H-indol-3-yl)-3-(thiophen-2-yl)-3-thioxopropan-1-one (4c) and guanidine
hydrochloride as a pale yellow solid in 78 % yield; mp 112–113 °C; 1H NMR (400 MHz, CDCl3): δ 8.57 (s, 1H,
2-H of indolyl), 7.95(s, 1H, N-heteroaryl CH), 7.81(d, J = 8.8 Hz, 2H), 7.58 (t, J = 8.4 Hz, 1H), 7.46 (d, J = 8.8 Hz,
4H, aromatic CH), 7.40–7.27 (m, 3H, aromatic CH), 7.25 (d, J = 8.8 Hz, 2H, aromatic CH), 5.61 (s, 2H, NH2), 5.47
(s, 2H, N-CH2); 13C NMR (100 MHz, CDCl3): δ 177.5, 176.3, 143.4, 138.3, 136.0, 129.2, 128.8, 128.0, 126.7,
125.7, 122.2, 122.1, 122.0, 112.9, 109.6, 100.1(CH) , 54.1(CH2) ; IR (KBr): 3335, 3178, 3025, 2671, 1579, 1516,
-1
1053, 887, 731 cm ; MS (ESI + ion): m/z = 382.9 (M+). Anal. Cacld for C24H17NOS: C, 72.22; H, 4.74; N, 14.65. Found: C, 72.21;
H, 4.73; N, 14.64.
4-(1-benzyl-5-bromo-1H-indol-3-yl)-6-phenylpyrimidin-2-amine (5d): Following the general procedure, compound 5d was
obtained from the reaction 1-(1-benzyl-5-bromo-1H-indol-3-yl)-3-phenyl-3-thioxopropan-1-one (4d) and
guanidine hydrochloride as a pale brown solid in 68 % yield; mp 174–176 °C; 1H NMR (400 MHz, CDCl3):
δ 8.55 (s, 1H, aromatic CH), 8.33 (s, 1H, 2-H of indolyl), 8.20–8.12 (m, 3H, aromatic CH), 8.06 (d, J = 8.0 Hz,
1H, aromatic CH next to Br), 7.75–7.71 (m, 2H, aromatic CH, N-heteroaryl CH), 7.66 (d, J = 7.2 Hz, 1H,
aromatic CH), 7.33–7.30 (m, 4H, aromatic CH), 7.14–7.10 (m, 2H, aromatic CH), 5.51 (s, 2H, NH2), 5.31 (s,
2H, N-CH2); 13C NMR (100 MHz, CDCl3): δ 163.8, 162.8, 162.7, 161.0, 137.3, 135.6, 133.1, 130.0, 128.2,
127.7, 127.1, 125.0, 124.8, 114.9, 113.5, 112.6, 100.2 (CH), 55.3(CH2); IR (KBr): 3334, 3109, 2975, 2851, 1578, 1512, 1052, 799,
733, 510 cm-1; MS (ESI + ion): m/z = 456.8 (M +). Anal. Cacld for C24H17NOS: C, 65.94; H, 4.21; N, 12.30. Found: C, 65.93; H,
4.18; N, 12.29.
1
H NMR 5a in DMSO-d6
13
C NMR 5a in DMSO-d6
1
H NMR 5b in DMSO-d6
13
C NMR 5b in DMSO-d6
1
H NMR 5c in CDCl3
13
C NMR 5c in CDCl3
1
H NMR 5d in CDCl3
13
C NMR 5d in CDCl3