Clobenzorex Hydrochloride

Molecular Formula: C16H18ClN*HCl Molecular Weight: 259.774 + 36.461 InChI= 1/C16H18ClN/c1-13(11-14-7-3-2-4-8-14)18-12-15-9-5-6-10-16(15)17/h2- 10,13,18H,11-12H2,1H3 IUPAC Name:  (+)-N-(o-Chlorobenzyl)--methylphenethylamine hydrochloride CAS Number: 18966-32-0 PubChem: 71675 Spectrometer: Varian Mercury 400 MHz Solvent: CD3OD Sample Concentration: 13.83 mg

Original 1D Proton Spectrum:

1D Proton Spectrum (6.31 ppm Maleic Acid, 4.89 ppm H₂O, TMS Subtracted):

1D Carbon Spectrum (168.4 ppm Maleic Acid, Deuterated Solvent, TMS Subtracted):

Automated VerifyIt Proton Assignments:

Automated VerifyIt Carbon Assignments:

Top 10 FindIt Molecular Structures Consistent With Molecular Formula and Proton Resonances:

The correct structure is at position 2.

 Best 10 structures in decreasing rating (structure ID shown in parentheses):
    1: 0.973205 (  203629)    2: 0.971108 (   71675)    3: 0.970448 (  202811)
    4: 0.966469 (  408921)    5: 0.966159 (  409716)    6: 0.959686 ( 3399675)
    7: 0.956398 (  408206)    8: 0.953191 ( 3862089)    9: 0.951410 (  411609)
   10: 0.945905 (  851538)
   

Top 10 FindIt Molecular Structures Consistent With Proton and Carbon Resonances:

The correct structure is at position 1.

 Best 10 structures in decreasing rating (structure ID shown in parentheses):
    1: 0.933222 (   71675)    2: 0.932409 (  211179)    3: 0.932318 (  203629)
    4: 0.930154 (  202811)    5: 0.927720 ( 9306444)    6: 0.927015 (  201367)
    7: 0.926608 (  714984)    8: 0.926380 ( 6918952)    9: 0.926371 ( 7316106)
   10: 0.926113 ( 3043270)
   

2D Multiplicity-Edited HSQC Spectrum:

Determined HSQC Correlations:

Top 10 FindIt Molecular Structures Consistent With Molecular Formula, Proton Resonances, and Protonated Carbon (HSQC) Resonances:

The correct structure is at position 2.

 Best 10 structures in decreasing rating (structure ID shown in parentheses):
    1: 0.931783 (  203629)    2: 0.929581 (   71675)    3: 0.929339 (  202811)
    4: 0.905630 (  408921)    5: 0.901098 (  409716)    6: 0.896999 ( 3399675)
    7: 0.867804 (  851538)    8: 0.867529 ( 8898284)    9: 0.849200 ( 3862089)
   10: 0.821569 ( 2826788)
   

2D DQF-COSY Spectrum:

AssembleIt HSQC & DQF-COSY Derived Carbon-Carbon Correlations:

2D HMBC Spectrum:

AssembleIt HSQC, HMBC & DQF-COSY Derived Correlations:

Comments:

Clobenzorex is an appetite suppressant for the treatment of obesity.

For a full structure elucidation, an ¹⁵N-HMBC spectrum would be highly desirable. A DQF-COSY spectrum should resolve vicinal proton-proton couplings down to 3 Hz. But FindIt identifies this molecule based on the carbon and proton resonances alone.











 
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Acetylsalicylic acid derivatives having a vinyl group EP 0732322 B1

• Fig. 1 is a ¹H-NMR spectrum of 2-acetyl-5-methacrylamidosalicylic acid obtained in Example 3.
• Fig. 2 is a ¹H-NMR spectrum of 2-acetyl-4-methacrylamidosalicylic acid obtained in Example 4.

http://www.google.com/patents/EP0732322B1?cl=en

Example 3Synthesis of 2-acetyl-5-methacrylamidosalicylic acid(1) 5-methacrylamidosalicylic acid (intermediate)
• [0069]
  5-aminosalicylic acid (50.0 millimole, 7.7 g), methacrylic anhydride (60.0 millimole, 9.3 g), and butylhydroxytoluene (20.0 mg) were suspended in dimethyl sulfoxide (50.0 ml). After sealing the suspension, its temperature was raised to 60° C by oil bath while stirring, and the suspension became homogeneous quickly. The mixture was further kept at 60° C for five hours while stirring to give a viscous liquid having dark brown color. The reaction was kept proceeding till the viscous liquid gave brown precipitate. The precipitate was filtrated, washed by dichloromethane to give brownish gray powder. The powder was recrystallized by a solution of 0.5% hydroquinone in methanol, and dried under a reduced pressure to give brownish gray crystal of 5-methacrylamidosalicylic acid: yield 9.27 g, 83.8%.
(2) 2-acetyl-5-methacrylamidosalicylic acid (the present invention)
• [0070]
  5-methacrylamidosalicylic acid (30 millimole, 6.7 g) was mixed with butylhydroxytoluene (20 mg), acetic anhydride (10.0 g), and acetic acid (15.0 g). After sealing the solution, its temperatures was raised to 60° C, and the solution was kept at 60°C for 30 min while stirring. Then, a mixture (1.0 g) of concentrated sulfuric acid (1 part) with hydrochloric acid (10 parts) was added to the solution, followed by raising its temperature to 90° C, and kept at 90° C for one hour to proceed the reaction. After the reaction was over, the solution was stood to cool to room temperature to give brown crystal. The crystal was filtrated, and recrystallized by a solution of 0.5% hydroquinone in methanol. Dried under a reduced pressure, 2-acetyl-5-methacrylamidosalicylic acid was obtained as pale reddish brown crystal having a needle shape: mp. 192.4°C, yield 2.54 g, 64.1%.
Elemental analysis (calculated as C₁₃H₁₃O₅N)
• [0071]

  	C	H	N
  calc.(%)	59.31	4.98	5.32
  exp.(%)	59.31	4.98	5.17

  
  

  • ¹H-NMR(DMSO-d₆, ppm)
  • δ: 13.11 (COOH), 9.99 (CONH), 8.27, 7.96, 7.93, 7.92, 7.16, 7.12 (C₆ H₃ ), 5.85, 5.55 (=CH₂ ), 2.23 (OCOCH₃ ), 1.96 (CH₃ ).
• [0072]
  A ¹H-NMR spectrum of the compound is shown in Fig. 1.
Example 4Synthesis of 2-acetyl-4-methacrylamidosalicylic acid(1) 4-methacrylamidosalicylic acid (intermediate)
• [0073]
  4-aminosalicylic acid was used as a starting material. The same procedures as the step (1) in Example 3 gave 4-methacrylamidosalicylic acid as yellow powder: yield 7.64 g, 68.9%.
(2) 2-acetyl-4-methacrylamidosalicylic acid (the present invention)
• [0074]
  4-methacrylamidosalicylic acid was used as a starting material. The same procedures as the step (2) in Example 3 gave 2-acetyl-4-methacrylamidosalicylic acid as pale yellow crystal having a needle shape: mp. 178.1°C; yield 3.51 g, 44.8%.
Elemental analysis (calculated as C₁₃H₁₃O₅N)
• [0075]

  	C	H	N
  calc.(%)	59.31	4.98	5.32
  exp.(%)	59.28	5.00	5.38

  
  

  • ¹H-NMR(DMSO-d₆, ppm)
  • δ: 12.86 (COOH), 10.18 (CONH), 7.93, 7.92, 7.88, 7.74, 7.65, 7.61 (C₆ H₃ ), 5.85, 5.60 (=CH₂ ), 2.25 (OCOCH₃ ), 1.95 (CH₃ ).
• [0076]
  A ¹H-NMR spectrum of the compound is shown in Fig. 2.

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1-(2-Hydroxy-5-(1-methoxyethyl)phenyl)-3-methylbut-2-en-1-one (1) and 1-(2-Hydroxy-5-methoxyphenyl)-3-methylbut-2-en-1-one (2)

1-(2-Hydroxy-5-(1-methoxyethyl)phenyl)-3-methylbut-2-en-1-one (1)

1-(2-Hydroxy-5-methoxyphenyl)-3-methylbut-2-en-1-one (2)

Journal of the Brazilian Chemical Society

Print version ISSN 0103-5053

J. Braz. Chem. Soc. vol.22 no.12 São Paulo Dec. 2011

http://dx.doi.org/10.1590/S0103-50532011001200021 

http://www.scielo.br/scielo.php?pid=S0103-50532011001200021&script=sci_arttext

1-(2-Hydroxy-5-(1-methoxyethyl)phenyl)-3-methylbut-2-en-1-one (1)

Yellow crystal; UV (MeOH) λ_max/nm (log ε): 220 (4.04), 274 (4.13), 344 (3.56); IR (KBr) ν_max/cm^-1: 3436 (OH), 1638 (C=O), 1580 (o-hidroxyacetone), 1486 (Ar); DIMS m/z (relative intensity): 256.9 [M + Na]⁺ (100), 235.0 [M + H]⁺ (10) in positive mode and 232.8 [M - H]^- (100) in negative mode (calc. for C₁₄H₁₈O₃: 234.0); for ¹H and ¹³C NMR spectroscopic data, see Table 1.

1-(2-Hydroxy-5-methoxyphenyl)-3-methylbut-2-en-1-one (2)

Yellow oil; UV (MeOH) λ_max/nm (log ε): 220 (4.04), 272 (4.08), 372 (3.58); IR (KBr) ν_max/cm^-1: 3513 (OH), 1643 (C=O), 1585 (o-hidroxyacetone), 1488 cm^-1 (Ar); DIMS m/z (relative intensity): 228.9 [M + Na]⁺ (100), 206.9 [M + H]⁺ (10) in positive mode and 204.8 [M - H]^- (100) in negative mode (calc. for C₁₂H₁₄O₃: 206,24); for ¹H and ¹³C NMR spectroscopic data, see Table 1.

Structural elucidation

1-(2-Hydroxy-5-(1-methoxyethyl)phenyl)-3-methylbut-2-en-1-one (1)

The DIMS spectrum showed a quasi-molecular ion peak at m/z 235 and 233 in [M + H]⁺ and [M - H]^- mode, respectively, corresponding to a molecular weight of 234 m/z, compatible with the molecular formula C₁₄H₁₈O₃.

The ¹H NMR (Table 1) and homonuclear correlation spectroscopy (COSY) NMR spectra showed the presence of an AB system at δ 7.5 (d, J 2.0 Hz, H-3), 7.2 (dd, J 8.6 and 2.0 Hz, H-5) and 6.80 (d, J 8.6 Hz, H-6); a vinyl hydrogen at δ 6.6 ppm (s, H-10); a methoxyl at δ 3.15 (s); two singlet at chemical shift 2.15 (H-13) and 1.99 (H-12), indicative of methyl groups in a isoprene system, and another methyl group at δ 1.2 ppm (d, J 6,3 Hz, H-8) coupled in COSY NMR to a methine signal at δ 4.2 (q, J 6.3 Hz, H-7). The ¹³C NMR spectrum (Table 1) showed four signals corresponding to CH₃ group with chemical shifts δ 56.0, 29.0, 25.2 and 22.5. The one corresponds to a methoxyl group as substituent at C-7, the third to methyl in C-8, finally, the second and four correspond to two methyl groups on double bond of isoprene system C-12 and C-13. The signal at δ 196.2 ppm was attributed to the carbonyl carbon, the signals δ 164.74, 134.3, 133.9, 127.7, 120.8 and 118.9 correspond to a six aromatic carbon atoms in a benzene ring. Besides this, the structure was elucidated with the help of 2D NMR techniques: heteronuclear single-quantum correlation spectroscopy (HMQC) and heteronuclear multiple-bond correlation spectroscopy (HMBC). The HMBC experiment showed correlations of C-1 (δ 164.74) with H-3 (δ7.5) and H-5 (δ 7.2); C-2 (δ 120.8) with H-6 (δ 6.80) and H-3 (δ 7.5), similarly, H-7 (δ 4.2) correlates with the C-4 (δ 133.9) and C-5 (δ 134.3). The position of de quaternary carbon C-4 was obtained through HMBC correlation with the CH₃ at (δ 1.2).

1-(2-Hydroxy-5-methoxyphenyl)-3-methylbut-2-en-1-one (2)

Comparing the spectroscopic data of the compound 1 and 2 and the literature,^18,22,23 it was possible to determine the structure of the second, with some differences between both. In the compound 2, the methoxyl group is bonded directly to aromatic ring C-4, that way, this carbon showed a higher chemical shift, C-4 (δ152.2), affecting the C-3 with δ 113.3. The other difference was the absence of carbons C-7 and C-8. The structures are showed in Figure 1.

Figure S1 - Click to enlarge

Figure S2 - Click to enlarge

Figure S3 - Click to enlarge

Figure S4 - Click to enlarge

Figure S6 - Click to enlarge

Figure S7 - Click to enlarge

Figure S8 - Click to enlarge

Figure S9 - Click to enlarge

Figure S10 - Click to enlarge

Figure S11 - Click to enlarge

Figure S12 - Click to enlarge

Figure S13 - Click to enlarge

Figure S14 - Click to enlarge

Figure S15 - Click to enlarge

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Olaparib オラパリブ 奥拉帕尼 (AZD-2281, trade name Lynparza)

Olaparib

オラパリブ

奥拉帕尼

syn.........http://newdrugapprovals.org/2014/12/19/olaparib-%E3%82%AA%E3%83%A9%E3%83%91%E3%83%AA%E3%83%96-azd-2281-trade-name-lynparza-az-first-in-class-parp-inhibitor-wins-eu-nod/

US 8183369

http://www.google.co.in/patents/US8183369

Mass Spectrum: MH+435

1H NMR (400 MHz. DMSO-d6) δ: 0.70 (m, 4H), 1.88 (br s, 1H), 3.20 (br s, 2H), 3.56 (m, 6H), 4.31 (s, 2H), 7.17 (t, 1H), 7.34 (dd, 1H), 7.41 (m, 1H), 7.77 (dt, 1H), 7.83 (dt, 1H), 7.92 (d, 1H), 8.25 (dd, 1H), 12.53 (s, 1H).

1H NMR spectrum of compound A (DMSO-d6) following the water treatment is shown in FIG. 1.

The powder XRD pattern of Compound A following the water treatment is shown in FIG. 2, which shows the compound is as Form A.

NMR PREDICTIONS

H-NMR spectral analysis

CAS NO. 763113-22-0, olaparib H-NMR spectral analysis

C-NMR spectral analysis

CAS NO. 763113-22-0, olaparib C-NMR spectral analysis

(S)-(+)-3-HYDROXY-2,2-DIMETHYLCYCLOHEXANONE

(S)-(+)-3-hydroxy-2,2-dimethylcyclohexanone

bp 85–87°C at 3.7 mm, [α]21D + 23.0° (CHCl3, c 2.0)

The spectral properties of (S)-(+)-3-hydroxy-2,2-dimethylcyclohexanone are as follows:

IR vmax (film) cm−1: 3470 (s), 1705 (s), 1120 (m), 1055 (s), 985 (s), 965 (m);

1H NMR (250 MHz, CDCl3) δ: 1.11 (s, 3 H), 1.15 (s, 3 H), 1.60–1.71 (m, 1 H), 1.76–1.86 (m, 1 H), 1.96–2.05 (m, 2 H), 2.16 (br s, 1 H), 2.35–2.45 (m, 2 H), 3.69 (dd, 1 H, J = 7.6, 2.9);

13C NMR (76 MHz, CDCl3) δ: 19.7, 20.7, 22.9, 29.0, 37.3, 51.3, 77.8, 215.3.

The optical purity of (S)-(+)-3-hydroxy-2,2-dimethylcyclohexanone can be determined by HPLC analysis.

The (S)-α-methoxy-α-trifluoromethylphenylacetate (MTPA ester) is prepared according to the reported procedure:3 HPLC analysis (Column, Nucleosil® 50-5, 25 cm × 4.6 mm; eluant, hexane : THF = 30 : 1, 1.03 mL/min; detected at UV 256 nm) retention time 35.6 min (98.0–99.4%) and 29.6 min (0.6–(2.0%). Therefore, the optical purity is determined to be 96.0–98.8% ee.

Analysis of the MTPA ester of this product by 250 MHz 1H NMR and capillary GLC (12.5 m, 5% methyl silicone column) failed to detect any more of the minor diastereomer than would have been expected from the purity (98% ee) of the MTPA-Cl employed.

NOTE….Intermediate is

2,2-dimethylcyclohexane-1,3-dione bp 92–97°C (4 mm)

37–38°C.

The spectra are as follows: 1H NMR (250 MHz, CDCl3) δ: 1.29 (s, 6 H), 1.93 (5 lines, 2 H, J = 6.5), 2.67 (t, 4 H, J = 6.9); 13C NMR (76 MHz, CDCl3) δ: 18.1, 22.3, 37.4, 61.8, 210.6.

Natural products synthesized from (S)-3-hydroxy-2,2-dimethylcyclohexanone

---

References and Notes

1. Department of Agricultural Chemistry, The University of Tokyo, Yayoi 1-1-1, Bunkyo-Ku, Tokyo 113, Japan.
2. Mekler, A. B.; Ramachandran, S.; Swaminathan, S.; Newman, M. S. Org. Synth., Coll. Vol. V 1973, 743, 3.
3. Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512.
4. Kieslich, K. “Microbial Transformations of Non-Steroid Cyclic Compounds;” Georg Thieme; Stuttgart, 1976, pp. 28–31.
5. Lu, Y.; Barth, G.; Kieslich, K.; Strong, P. D.; Duax, W. L.; Djerassi, C. J. Org. Chem. 1983, 48, 4549.
6. Mori, K.; Mori, H. Tetrahedron 1985, 41, 5487.
7. Yanai, M.; Sugai, T.; Mori, K. Agric. Biol. Chem. 1985, 49, 2373.
8. Mori, K.; Watanabe, H. Tetrahedron 1986, 42, 273.
9. Mori, K.; Nakazono, Y. Tetrahedron 1986, 42, 283.
10. Mori, K.; Mori, H.; Yanai, M. Tetrahedron 1986, 42, 291.
11. Mori, K.; Tamura, H. Tetrahedron 1986, 42, 2643.
12. Sugai, T.; Tojo, H.; Mori, K. Agric. Biol. Chem. 1986, 50, 3127.
13. Mori, K.; Mori, H. Tetrahedron 1986, 42, 5531.
14. Mori, K.; Mori, H. Tetrahedron 1987, 43, 4097.
15. Mori, K.; Komatsu, M. Liebigs Ann. Chem. 1988, 107.

 
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