Zhang et al.
OH, NH ). The H NMR data of this compound are in good Funding
5
1
2
2
3
agreement with the reported data.
The author(s) disclosed receipt of the following financial sup-
port for the research, authorship, and/or publication of this
paper: This research was supported by a grant from Chongqing
Science and Technology Commission (cstc2019jscx-
msxmX0096) and a grant from the Undergraduate Everyone
Innovative Program of the School of Pharmacy of Chongqing
Medical University (DXSZCXM201905).
Synthesis of
1
-[[(3-hydroxytricyclo[3.3.1.1(3,7)]dec-1-
yl)amino]acetyl]-2-pyrrolidine carbonitrile
Vildagliptin) (1)
(
3
-Aminoadamantanol (3) (3g, 18mmol), THF (21mL),
potassium carbonate (10g, 72.5mmol), and potassium
iodide (0.25g, 1.5mmol) were added to a 150-mL three-
Supplemental material
neck round bottom flask which was equipped with a con- Supplemental material for this paper is available online.
denser, a thermometer, and a constant pressure funnel. The
mixture was heated to 40°C under stirring and then the
compound 2 (3g, 16.5mmol) dissolved in THF (22mL) References
was added dropwise over 1.5h. The reaction mixture was
then stirred at 40°C for 1h and then at reflux for 0.5h. The
reaction was monitored by thin layer chromatography
1
. Cho NH, Shaw JE, Karuranga S, et al. Diabetes Res Clin
Pract 2018; 138: 271–281.
2. Fonseca V, Schweizer A, Albrecht D, et al. Diabetologia
(
TLC; 5% CH OH–CH Cl ). After completing the reac-
2007; 50: 1148–1155.
3
2
2
3
. Mutius EV and Peter NLS. Horm Metab Res 2006; 38: 423–
28.
tion, the hot mixture was filtered and the filter cake was
washed with hot 2-butanone (3×20mL). The collected
filtrate was concentrated under vacuum and stirred while
slowly cooling. After the mixture became viscous, it was
stirred in an ice bath. The resulting white crystalline solid
was filtered, washed with ethyl acetate (3×20mL), and
then dried at 45°C under vacuum to afford vildagliptin (1)
4
4
5
. Mathieu C. Diabetes Obes Metab 2009; 11: 9–17.
. Mcinnes G, Evans M, Prato SD, et al. Diabetes Obes Metab
2
015; 17: 1085–1092.
. Tahrani AA, Piya MK and Barnett AH. Adv Ther 2009; 26:
49–262.
6
7
2
. Monami M, Dicembrini I and Mannucci E. Nutr Metab
Cardiovas 2014; 24: 689–697.
(
4.1g, 82%) as a white solid; m.p. 148–150°C (litera-
2
4
−1
ture —m.p. 150°C); IR (KBr, cm ): 3293, 2915, 2848,
8. He H, Tran P, Yin H, et al. Drug Metab Dispos 2009; 37:
536–544.
9. Henness S and Keam SJ. Drugs 2006; 66: 1989–2001.
0. Villhauer EB. PCT Int Appl. WO 01/96295 A3. Chem Abstr
1
2
1
3
1
241, 1656, 1405; H NMR (600MHz, DMSO-d ): δ
6
.41–1.49 (m, 14H, CH ), 1.97–2.02 (m, 2H, OH, NH),
2
1
.44–3.63 (m, 2H, COCH ), 4.72–4.74 (dd, J=7.7, 3.4Hz,
2
2
001; 136: 37503.
11. Deng Y, Wang AM, Tao Z, et al. Lett Org Chem 2014; 11:
80–784.
12. Klimova NV. Khimiko-Farmatsevti cheskii Zhurnal 1986;
0: 810–815.
13. Mlinarić-Majerski K, Margeta R and Veljković J. Synlett
005; 13: 2089–2091.
4. Zhang LF, Zhu JD, Wang M, et al. Chin J Mod Appl Pharm
016; 33: 683–686.
5. Singh SK and Manne NPM. Beilstein J Org Chem 2008; 4:
–5.
6. Yamaguchi K and Mizuno N. Cheminform 2010; 42: 1480–
483.
7. Kuo CW, Zhu JL, Wu JD, et al. Chem Commun 2007; 38:
01–303.
8. Hanada S, Motoyama Y and Nagashima H. Eur J Org Chem
008; 24: 4097–4100.
9. Feng F, Cheng YJ, Peng J, et al. Chem Res Appl 2013; 25:
94–199.
H, CHCN), 2.10–2.14 (m, 4H, CH ), 3.26–3.32 (m, 2H,
2
1
3
NCH ); C NMR (125MHz, DMSO-d ): δ 25.2, 30.6,
2
6
7
3
4
5.5, 39.7, 39.9, 40.0, 40.1, 40.3, 41.5, 43.5, 44.9, 45.6,
20
6.6, 53.2, 68.2, 119.8, 171.1. [α] =−0.09 (c 1g/100mL,
D
2
2
D
0
2
5
MeOH) (literatur —[α] =−0.087 (c 1g/100mL,
1
13
MeOH)); The H and C NMR data of this compound are
2
11
in good agreement with the reported data.
1
1
1
1
1
1
2
2
OP test
1
Compound 2 (0.25g, 1.448mmol) was dissolved in chloro-
form to ensure that the solution was clear and transparent with-
out any solid particles. Volumetric flasks (25mL) were used
for volumetric determination and then tested. The WZZ-2B
automatic polarimeter (λ=589.3nm) was allowed to preheat
for at least 30min after being switched on. Three sample tubes
were each loaded with chloroform and then put into the pola-
rimeter to set zero. The sample tube was then rinsed with the
test solution 2–3 times before recording specific solution. The
1
3
2
1
0. Ferreira SLC, Bruns RE, Silva EGPD, et al. J Chromatogr A
2007; 1158: 2–14.
solution to be tested was injected into the sample tube at 20°C 21. Wang YA and Ma YZ. Fine Chem Intermediat 2010; 40:
to measure the OP. This process was repeated three times. The
values were recorded and the averages were calculated.
27–31.
2
2
2. Hu XN, Liao Q, Zhang H, et al. CN Patent 108059601A,
2
018.
3. Xie BY, Guo JW, Liu S, et al. Chin J Org Chem 2011; 31:
86–489.
Declaration of conflicting interests
4
The author(s) declared no potential conflicts of interest with respect 24. Stephen W. WO Patent 0,084,383, 2008.
to the research, authorship, and/or publication of this paper.
25. Yang HJ. J Strait Pharm 2019; 31: 77–79.