4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4- thioxoimidazolidin-l-yl)butanoic acid

Example 14; 4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4- thioxoimidazolidin-l-yl)butanoic acid

RU59063 (145 mg, 0.38 mmol) was dissolved in 2 mL DMF, charged with PDC (1.4 g, 3.7 mmol) and stirred for 48 hours, upon which time the mixture was quenched with 10 mL 1 M HCL and extracted into Et₂0 (5 X 25 mL). The combined organic layers were washed with brine (1 X 100 mL), dried with Na₂S0₄ and concentrated down to yield 135 mg (90% yield) pure product.


H NMR (300 MHz, CDC1₃) δ 7.94 (d, J= 8.3, 1H), 7.88 (s, 1H), 7.77 (d, J= 8.2, 1H), 3.82 - 3.65 (m, 2H), 2.50 (s, 2H), 2.14 (s, 2H), 1.59 (s, 6H);


¹³C NMR (126 MHz, CDC1₃) δ 178.6, 177.4, 175.3, 175.2, 137.1, 135.2, 133.5 (q, J = 32.1), 132.1, 127.0 (q, J= 4.7), 121.8 (q, J= 276.2), 114.9, 1 10.1, 65.2, 43.3, 31.7, 23.1 ;


 LRMS (ESI) 421.2
(M+Na)⁺.

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2-(2-(4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo- 2-thioxoimidazolidin-l-yl)butanamido)ethoxy)ethyl 2-(adamantan-l-yl)acetate

   Example 5; 2-(2-(4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo- 2-thioxoimidazolidin-l-yl)butanamido)ethoxy)ethyl 2-(adamantan-l-yl)acetate



To a 1 dram vial with stirbar was charged 4-(3-(4-cyano-3-
(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-l-yl)butanoic acid (10.0 mg, 0.025 mmol), EDC (7.0 mg, 0.038 mmol), HOBt (6.0 mg, 0.375 mmol), and 0.35 mL dichloromethane. After 15 minutes of stirring 2-(2-aminoethoxy)ethyl 2-(adamantan-l-yl)acetate (8.0 mg, 0.027 mmol) was added and the mixture left stir for 16 h upon which the mixture was diluted with 1 mL dichloromethane and washed with 10% aq. citric acid (2 X 1 mL), and saturated a₂C03 (2 X 1 mL). The organic layer was dried with Na₂S0₄ and concentrated down to yield a crude oil which was purified by silica gel chromatography (dichloromethane to 19: 1 dichloromethane: MeOH) to yield 5 mg (30% yield) of pure product as an amber oil.

H NMR (500 MHz, CDC1₃) δ 7.93 (d, J= 8.3, 1H), 7.87 (d, J= 1.7, 1H), 7.75 (dd, J= 1.9, 8.3, 1H), 6.04 (t, J= 5.1, 1H), 4.25 - 4.14 (m, 2H), 3.79 - 3.71 (m, 2H), 3.68 - 3.61 (m, 2H), 3.55 (t, J = 5.0, 2H), 3.49 - 3.40 (m, 2H), 2.32 (t, J = 6.7, 2H), 2.14 (dt, J = 6.8, 14.4, 2H), 2.08 (s, 2H), 1.95 (s, 4H), 1.70-1.66 (m, 4H), 1.65-1.55 (m, 13 H);  


¹³C NMR (126 MHz, CDCI₃) δ 178.6, 175.5, 172.0, 171.8, 137.3, 135.3, 133.6 (q, J = 33.4), 132.3, 127.2 (q, J= 4.7), 121.0 (q, J = 274.0), 115.0, 110.1 (q, J= 2.2), 69.7 69.3, 65.4, 62.7, 49.0, 43.7, 42.5, 39.4, 36.8, 33.0, 33.0, 28.7, 23.7, 23.2;


LRMS (ESI) 662.4 (M+H)⁺.

http://www.google.com/patents/WO2013170147A1?cl=en






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1H NMR spectra of the encapsulation of ubiquitin within coordination spheres.

(a) Ubiquitin ligand 2a. (b) Ligand 1a. (c) Ubiquitin-containing sphere 3a after treating ubiquitin ligand 2a with ligand 1a (30 equiv) and Pd(NO3)2 (17 equiv) in D2O/CD3CN (1:1, 0.5 ml) at 45 °C for 3 h. Downfield shifts of the signals of the pyridine rings (Ha, Hb) confirm the formation of Pd-pyridine bonds in coordination sphere 3a, and the simple spectrum indicates the quantitative self-assembly of ubiquitin-containing sphere 3a. All spectra recorded at 500 MHz, inD2O:CD3CN=1:1, at 300 K.http://www.nature.com/ncomms/journal/v3/n10/fig_tab/ncomms2093_F2.html

13 C NMR...One for your eye

Ethanal or AcetaldehydeEthanoic acid or Acetic acidEthanol or Ethyl alcohol

Since all three preceding C-13 spectra are fully proton decoupled, the carbon atoms appear as narrow singlets (single peaks). Note that the carbons in methyl groups (–CH₃, indicated as C2 next to peaks) of all three compounds have a chemical shift rather upfield (close to the right) in the spectra not too far from about 20 ppm. The carbon in themethylene group (–CH₂–, indicated as C1) in ethanol is brought further downfield to 58 ppm because that carbon is bonded directly to the oxygen in the hydroxyl group (–OH). Note that the carbonyl group (–CO–, indicated as C1) carbons in acetaldehyde and acetic acid are downfield at the left side of the spectrum, the carbonyl region between about 160 and 220 ppm.

Synthesis and characterization of maleimide-functionalized polystyrene-SiO2/TiO2 hybrid nanocomposites by sol–gel process Ramesh S, Sivasamy A, Kim JH - Nanoscale Res Lett (2012)

Synthesis and characterization of maleimide-functionalized polystyrene-SiO2/TiO2 hybrid nanocomposites by sol–gel process

Ramesh S, Sivasamy A, Kim JH - Nanoscale Res Lett (2012)http://www.nanoscalereslett.com/content/7/1/350

Nanoscale Research Letters 2012, 7:350  doi:10.1186/1556-276X-7-350

Synthesis of N-chloromethyl maleimide

N-chloromethyl maleimide was prepared in two steps[1-4]. In the first step, N-ethylmaleimide was prepared using a suspension of 24.5 g (0.25 mol) of maleimide in 20.3 ml of 37% formalin at 30°C with the addition of 0.75 ml of 5% NaOH over a period of 30 min and allowing it to stand for 3 h and then filtered. The crude product yield of 75%, m.p = 103°C, was recrystallized using ethyl acetate

1 H NMR (CDCl3), δ (ppm) = 3.45 (S, 1 H), 5.09 (S, 2 H), and 6.76 (S, 2 H)

and 13 C NMR, δ (ppm) = 61.11, 134.71, and 70.25 (C = O).

In the second step, phosphorous trichloride of 4.3 g (0.03 mol) was added to the solution of 10 g (0.08 mol) of N-methyl maleimide in 50 ml of acetone in an ice bath. Then, the solution was stirred for 30 min and then concentrated at the aspirator. The resulting partly crystalline residue was precipitated by adding 50 ml of ice-cold water and filtered. The product N-chloromethyl maleimide was recrystallization from benzene-petroleum ether mixture. The sequence of reaction N-chloromethyl maleimide is presented in Figure1

1HNMR (CDCl3) δ (ppm) = 5.32 (S, 2 H), and 6.84 (S, 2 H);

13 C NMR δ (ppm) = 44.28, 135.27, and 168.17 (C = O).

FTIR spectra. (a) N-methylolmaleimide, (b) N-chloromethyl maleimide, and (c) maleimide-functionalized polystyrene.

Brivanib alaninate  is a new oncology therapy with potential applications against a wide variety of tumor types and several stages of disease progression

Brivanib alaninate ブリバニブアラニンエステル

SYN...........http://newdrugapprovals.org/2014/12/23/brivanib-alaninate-%E3%83%96%E3%83%AA%E3%83%90%E3%83%8B%E3%83%96%E3%82%A2%E3%83%A9%E3%83%8B%E3%83%B3%E3%82%A8%E3%82%B9%E3%83%86%E3%83%AB/

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/op500126u

http://pubs.acs.org/doi/full/10.1021/op500126u

(S)-((R)-1-(4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-yl)-2-aminopropanonate (1)

1H NMR (400 MHz, CDCl3) 8.31 (1 H, s), 7.83 (1 H, s), 7.25 (1 H, s), 7.00 (1 H, d, J= 8.6 Hz), 6.95 (1 H, dd, J = 15.4, 8.6 Hz), 6.28 (1 H, s), 5.36–5.30 (1 H, m), 4.08–4.00 (2 H, m), 3.57 (1 H, dd, J = 14.0, 6.9 Hz), 2.47 (3 H, s), 2.40 (3 H, s), 1.66 (3 H, s), 1.38 (3 H, d, J = 6.4 Hz), 1.35 (3 H, d, J = 7.1 Hz).

(S)-((R)-1-(4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-yl)-2-(benzyloxycarbonylamino)propanonate

1H NMR (400 MHz, CDCl3) 8.17 (1 H, br s), 7.84 (1 H, s), 7.41 (1 H, s), 7.35–7.28 (5 H, m), 7.03 (1 H, d, J = 8.6 Hz), 6.95 (1 H, t, J = 7.7 Hz), 6.30 (1 H, s), 5.36–5.32 (2 H, m), 5.11 (2 H, br s), 4.43–4.40 (1 H, m), 4.02–3.99 (2 H, m), 2.46 (3 H, s), 2.41 (3 H, s), 1.44 (3 H, d, J = 7.2 Hz), 1.38 (3 H, d, J = 7.2 Hz).

HSQC - TOCSY 3 Heptanone

One can see the two spin systems on either side of the carbonyl group, color coded in yellow and pink. The second panel shows an expansion of the region within the red square of the first panel. Here we can separate the overlapping quartet and triplet for the methylene protons on either side of the carbonyl group.

 
 
Protons a, b, c and d constitute one spin system, an unbroken network of coupled protons.  The ethyl group, e and f, constitutes a second, separate spin system, because there is no coupling between a and e, across the carbonyl.
In a COSY spectrum, CH₂ a would show a correlation to CH₂ b.   In a TOCSY spectrum, it would also show correlations to CH₂s c and d.  


 








 

 


 
 


RAMAN

 




13 C NMR


 



MASS

 



IR








 







1H NMR









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