tert-Butyl 4-(2,3-diaminophenyl)piperazine-1- carboxylate

tert-Butyl 4-(2,3-diaminophenyl)piperazine-1- carboxylate (4)

1H NMR (400 MHz, CDCl3), δ in ppm = 6.68 (t, 1H), 6.59 (d, J = 8.8 Hz, 1H), 6.55 (d, J = 7.6 Hz, 1H), 3.56 (br s, 8H), 2.83 (s, 4H), 1.49 (s, 9H). This is consistent with literature data.1

Small molecule piperazinyl-benzimidazole antagonists of the gonadotropin-releasing hormone (GnRH) receptor

 

Richard Fjellaksel,*abc  Marc Boomgaren,c  Rune Sundset,ad  Ira H. Haraldsen,e  Jørn H. Hansenc  and Patrick J. Rissefg 

 Author affiliations

*Corresponding authors

aMedical Imaging Group, Department of Clinical Medicine, UiT The Arctic University of Norway, 9037 Tromsø, Norway
E-mail: richard.fjellaksel@uit.no

bDrug Transport and Delivery Group, Department of Pharmacy, UiT The Arctic University of Norway, 9037 Tromsø, Norway

cOrganic Chemistry Group, Department of Chemistry, UiT The Arctic University of Norway, 9037 Tromsø, Norway

dPET imaging center, division of diagnostics, UNN – University Hospital of North-Norway, 9038 Tromsø, Norway

eDepartment of neuropsychiatry and psychosomatic medicine, Oslo University Hospital, Oslo, Norway

fRealomics SFI, Department of Chemistry, University of Oslo, PO BOX 1033, Oslo 0371, Norway

gNorsk Medisinsk Syklotronsenter AS, Postboks 4950 Nydalen, 0424 Oslo, Norway

Abstract

In this communication, we report the synthesis and characterization of a library of small molecule antagonists of the human gonadotropin releasing hormone receptor based upon the 2-(4-tert-butylphenyl)-4-piperazinyl-benzimidazole scaffold via Cu-catalysed azide alkyne cycloaddition. Our main purpose was to find a more soluble compound based on the WAY207024 lead with nanomolar potency to inhibit the GnRH receptor. A late stage diversification by the use of click chemistry was, furthermore developed to allow for expansion of the library in future optimisations. All compounds were tested in a functional assay to determine the individual potency of inhibiting stimulation of the receptor by the endogenous agonist GnRH. In conclusion, we found that compound 8ashowed improved solubility compared to WAY207024 and nanomolar affinity to GnRH receptor.

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References 1. Pelletier, J. C.; Chengalvala, M.; Cottom, J.; Feingold, I.; Garrick, L.; Green, D.; Hauze, D.; Huselton, C.; Jetter, J.; Kao, W.; Kopf, G. S.; Lundquist, J. T. t.; Mann, C.; Mehlmann, J.; Rogers, J.; Shanno, L.; Wrobel, J., 2-phenyl-4-piperazinylbenzimidazoles: orally active inhibitors of the gonadotropin releasing hormone (GnRH) receptor. Bioorganic & medicinal chemistry 2008, 16 (13), 6617-40.

Oxidant- and hydrogen acceptor-free palladium catalyzed dehydrogenative cyclization of acylhydrazones to substituted oxadiazoles

Oxidant- and hydrogen acceptor-free palladium catalyzed dehydrogenative cyclization of acylhydrazones to substituted oxadiazoles

Org. Chem. Front., 2018, Advance Article
DOI: 10.1039/C7QO00749C, Research Article

Qiangqiang Jiang, Xinghui Qi, Chenyang Zhang, Xuan Ji, Jin Li, Renhua Liu

An efficient method for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles has been developed through palladium(0) catalyzed dehydrogenative cyclization of N-arylidenearoylhydrazides without oxidants and hydrogen acceptors.

Oxidant- and hydrogen acceptor-free palladium catalyzed dehydrogenative cyclization of acylhydrazones to substituted oxadiazoles

Qiangqiang Jiang,a  Xinghui Qi,a  Chenyang Zhang,a  Xuan Ji,a  Jin Li*b  and  Renhua Liu*a 

*Corresponding authors

aSchool of Pharmacy, East China University of Science and Technology, Meilong Road 130, Shanghai 200237, China
E-mail: liurh@ecust.edu.cn

bChina Catalyst Holding Co., Ltd, Jingjiu Road 3, Chemical Park, Songmu Island, Puwan New District, Dalian 116699, China
E-mail: lijin@china-catalyst.com

Abstract

An efficient method for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles has been developed through palladium(0) catalyzed dehydrogenative cyclization of N-arylidenearoylhydrazides. By using this method, a wide range of functionalized and potentially biologically relevant 1,3,4-oxadiazole-containing compounds have been accessed in moderate to high isolated yields. The dehydrogenative cyclization process is characterized by the nonuse of any sacrificing hydrogen acceptors or oxidants and hydrogen gas as the only by-product, and therefore circumvents the recurring problems of over-oxidation and the compatibility with easily oxidizable functionalities in oxidation protocols.

109.6 mg, 87 % yield; White solid,

1H NMR (400 MHz, CDCl3) δ 8.13 – 8.08 (m, 2H), 8.06 (d, J = 8.7 Hz, 2H), 7.52 (m, 3H), 7.01 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H);

13C NMR (100 MHz, CDCl3) δ 164.51, 164.10, 162.33, 131.54, 129.03, 128.67, 126.80, 124.05, 116.38, 114.50, 55.46; M.p. 145-146 oC.

2-(4-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole12

1H NMR CDCL3

http://pubs.rsc.org/en/Content/ArticleLanding/2018/QO/C7QO00749C#!divAbstract

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Learn spectroscopy,1-chloro-2,2- dimethyl propane.PROBLEM 2

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1-chloro-2,2- dimethyl propane.
(C₅H₁₁Cl)

13C NMR

This ¹³C spectrum exhibits resonances at the following chemical shifts:

Shift (ppm)

57.3

33.1

27.3

NMR IS EASY

EVEN MOM CAN TEACH YOU






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“ORGANIC SPECTROSCOPY INT” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

3.4. 1,2,3,4-Tetra-O-Acetyl-β-d-Mannuronic Acid

Laura Beswick

2nd degree connection

PhD Student at Keele University

Gavin J. Miller

2nd degree connection

Lecturer in Organic Chemistry at Keele University

3.4. 1,2,3,4-Tetra-O-Acetyl-β-d-Mannuronic Acid (4)

To a vigorously stirred solution of 1,2,3,4-tetra-O-acetyl-β-d-mannopyranose (3) (1.5 g, 4.30 mmol, 1.0 equiv.) in dichloromethane (20 mL) and water (10 mL) was added (2,2,6,6-tetramethylpiperidin-1-yl)oxyl radical (TEMPO) (336 mg, 2.2 mmol, 0.50 equiv.) and [bis(acetoxy)iodo]benzene (BAIB) (6.9 g, 21.5 mmol, 5.00 equiv.). The solution was stirred at RT for 5 h, whereupon TLC analysis (hexane/ethyl acetate, 1/1) showed complete conversion of starting material to a baseline Rf value spot. The reaction was quenched with aqueous Na2S2O3 solution (10% w/v, 30 mL), the organic layer removed and the aqueous layer acidified to pH 3 using 1M HCl, followed by extraction with ethyl acetate (2 × 30 mL). The organic extracts were combined, dried (MgSO4), filtered and concentrated in vacuo to afford 1,2,3,4-tetra-O-acetyl-β-d-mannuronic acid (4) as a white solid (1.2 g, 3.3 mmol, 75%). Rf = 0.81 (dichloromethane/methanol, 9/1);

 1H-NMR (300 MHz, CDCl3) δH5.96 (1H, d, J = 1.5 Hz, H1), 5.50 (1H, dd, J = 3.2, 1.5 Hz, H2), 5.48 (1H, appt, J = 9.1 Hz, H4), 5.21 (1H, dd, J = 9.1, 3.2 Hz, H3), 4.2 (1H, d, J = 9.1 Hz, H5), 2.21 (3H, s, C(O)CH3), 2.13 (3H, s, C(O)CH3), 2.10 (3H, s, C(O)CH3), 2.04 (3H, s, C(O)CH3).

 13C-NMR (100 MHz, CDCl3) δC 169.9 (C=O), 169.7 (C=O), 169.5 (C=O), 169.4 (C=O), 168.2 (C=O), 89.4 (C1), 72.3 (C5), 69.3 (C3), 66.9 (C2), 65.9 (C4), 20.4 (C(O)CH3), 20.4 (C(O)CH3), 20.3 (C(O)CH3), 20.2 (C(O)CH3); 

FT-HRMS NSI (ES−) m/z Found: (M−H)− 361.0767, C14H17O11 requires 361.0776; FT-IR vmax/cm−1 2986 (O–H), 1751 (C=O).

Molbank 2017, 2017(3), M947; doi:10.3390/M947

Communication

1,2,3,4-Tetra-O-Acetyl-β-d-Mannuronic Acid

Laura Beswick and Gavin J. Miller *

Lennard-Jones Laboratory, School of Chemical and Physical Sciences, Keele University, Keele, Staffordshire ST5 5BG, UK

*

Correspondence: Tel.: +44-1782-734442

Received: 3 July 2017 / Accepted: 11 July 2017 / Published: 14 July 2017

Abstract

: 

1,2,3,4-Tetra-O-acetyl-β-d-mannuronic acid was synthesized in three steps from commercial d-mannose in 21% yield. Regioselective 6-O-tritylation followed by per-acetylation and 6-OTr removal using HBr/AcOH gave the required primary alcohol substrate, which was then oxidised to the target compound using TEMPO/BAIB. None of the synthetic steps required column chromatography and the product was fully characterized by 1H-NMR, 13C-NMR, 2D NMR, MS and IR.

http://www.mdpi.com/1422-8599/2017/3/M947/htm

Keele University, Keele, Staffordshire

Lennard-Jones Laboratory, School of Chemical and Physical Sciences, Keele University,

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“ORGANIC SPECTROSCOPY INT” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

Learn spectroscopy, Valeric acid or pentanoic acid. PROBLEM 1

.



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Product Name: Valeric acid


CAS:109-52-4




valeric acid

pentansäure

acide pentanoic

ペンタン酸

109-52-4 CAS

C5H10O2














Valeric acid, or pentanoic acid.


This 13C spectrum exhibits resonances at the following chemical shifts, and with the multiplicities indicated:


Shift (ppm)

Mult.

180.8

S

33.8

T

26.8

T

22.4

T

3.58

Q

(C5H10O2)



A= 13.4

B=22.4

C=26.8

D=33.8

E=180.6














1H NMR BELOW


t=0.78

m=1.22

m=1.46

t=2.2

s=11.8

















NMR IS EASY

EVEN MOM CAN TEACH YOU







2D [1H,1H]-TOCSY

Concentration: 100 mM

temperature: 298 K

pH: 7.4









1D DEPT90

Concentration: 100 mM

temperature: 298 K

pH: 7.4















1D DEPT135

Concentration: 100 mM

temperature: 298 K

pH: 7.4







2D [1H,13C]-HSQC

Concentration: 100 mM

temperature: 298 K

pH: 7.4










2D [1H,13C]-HMBC

Concentration: 100 mM

temperature: 298 K

pH: 7.4

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19F NMR

19F NMR

According to quantum mechanics, any nucleus is magnetically active if it possess a nonzero angular moment, P, which gives rise to a nuclear magnetic moment, µ, capable of interacting with an external magnetic field (Eq. 1).

(1)                                 µ = γP

The magnetogyric ratio, γ, is the ratio of magnet moment to angular momentum. It relates the magnetic resonance (MR) frequency of a nuclide and the strength, or sensitivity of response of interaction of the nuclide when it is subjected to an external magnetic field. The 1H nucleus has the largest γ value (26.752 107 rad T-1 s-1) of stable isotopes on the NMR periodic table, making it the most sensitive to nuclear resonance excitation. The 19F nuclide comes next with a high magnetogyric ratio (25.18 107 rad T-1 s-1) at 94% of 1H, and has the advantage of 100% natural abundance. In combination, the result is a high relative sensitivity of 83% for fluorine.

With a dedicated Thermo Scientific™ picoSpin™ 45 19F NMR spectrometer, measuring19F NMR spectra in a bench-top instrument is as easy as acquiring proton spectra from the picoSpin™ 45 1H NMR spectrometer. A dedicated 19F spectrometer is tuned to the fluorine Larmor frequency (42.4 MHz) to yield the highest sensitivity for this nuclide. This application note presents 19F NMR spectra acquired from highly fluorinated small organic compounds, demonstrating the wealth of spectral information obtained from a bench-top picoSpin™ 45 19F NMR spectrometer.

Figure 1. Full 19F NMR (42.4 MHz) spectrum of hexaflourobenzene (neat); 25 scans

Figure 2. Full 19F NMR (42.4 MHz) spectrum of octafluorotoluene (neat); 36 scans

Figure 3. Full 19F NMR (42.4 MHz) spectrum of 2H,3H-decafuoropantane (neat)

Figure 4. Full 19F NMR (42.4 MHz) spectrum of hexafluoroisopropanol in trifluorotoluene (70:30 v/v)

Figure 5. Full 1H NMR (45 MHz) spectrum of hexafluoroisopropanol in trifluorotoluene (70:30 v/v)