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DR ANTHONY MELVIN CRASTO,WorldDrugTracker, helping millions, A 90 % paralysed man in action for you, I am suffering from transverse mylitis and bound to a wheel chair, With death on the horizon, nothing will not stop me except God................DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 25Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK GENERICS at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution

Thursday, 8 January 2015

2-Trimethylammonio-6-hydroxy-benzaldehyde oxime chloride

Peak assignment in the ¹H-NMR spectrum of 10 mM TAB2OH in 20 mM phosphate-pyrophosphate (+ 0.1 M NaCl) ²H₂O buffer, pH 5

2-Trimethylammonio-6-hydroxy-benzaldehyde oxime chloride (TAB2OH)

To a stirring solution of 4.19 (90 mg, 0.50 mmol) in dichloromethane (0.2 ml) at 0°C was added methyl trifluoromethansulfonate (62 μl, 0.55 mmol). The reaction was allowed to warm to room temperature and stirred for 40 h. The precipitate formed was collected by filtration washing with excess dichloromethane to afford 101 mg of the pure triflate salt as a white solid (59%). The salt was dissolved in acetonitrile and a solution of tetrahexylammonium chloride in acetonitrile was added to precipitate the pure chloride salt as a white solid.
¹H-NMR (600 MHz, d₆-DMSO) δ 11.74 (s, 1 H), 10.95 (s, 1 H), 8.34 (s, 1 H), 7.45 (t, J 8.4 Hz, 1 H), 7.39 (d, J 8.4 Hz, 1 H), 7.26 (d, J 8.2 Hz, 1 H), 3.68 (s, 9 H).

¹³C-NMR (150.9 MHz, d₆-DMSO) δ 158.9, 145.6, 145.5, 130.6, 117.5, 113.5, 111.3, 57.2.

HRMS (M⁺) expected, 195.1133; found, 195.1130.

http://www.biochemj.org/bj/450/bj4500231add.htm

MORE..............
2-Dimethylamino-6-hydroxy-benzaldehyde oxime (4.19)

To a stirring solution of 2-dimethylamino-6-methoxymethoxy-benzaldehyde oxime (14 mg, 0.06 mmol) in methanol (0.2 ml) at room temperature was added a 4 M solution of hydrogen chloride in dioxane (0.2 ml, 0.8 mmol). The reaction was heated to 70°C for 1 h and then cooled to room temperature and the solvent was blown off with nitrogen. The crude material was purified by flash chromatography over silica gel eluting with dichloromethane to afford 10 mg of pure product as a white solid (91%). ¹H-NMR (600 MHz, [²H]chloroform) δ 10.06 (s, 1 H), 8.65 (s, 1 H), 7.21 (t, J 8.1 Hz, 1 H), 7.11 (s, 1 H), 6.66 (d, J 8.2 Hz, 1 H), 6.60 (d, J 8.0 Hz, 1 H), 2.73 (s, 6 H). ¹³C-NMR (150.9 MHz, [²H]chloroform) δ 158.5, 154.8, 151.4, 131.6, 111.3, 110.2, 109.8, 45.6. HRMS (MH⁺) expected, 181.0971; found, 181.0983.

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

.........

1-pentyne

...............

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

A graph theory approach to structure solution of network materials from two-dimensional solid-state NMR data

A graph theory approach to structure solution of network materials from two-dimensional solid-state NMR data

Darren H. Brouwer and Kevin P. Langendoen

CrystEngComm, 2013,15, 8748-8762
DOI: 10.1039/C3CE41058G http://pubs.rsc.org/en/journals/articlecollectionlanding?sercode=ce&themeid=acb8167b-70f0-41f9-8ee8-e03bcf1367b9

An NMR crystallography strategy is presented for determining crystal structures of network materials such as zeolites from a single 2D NMR spectrum using concepts from graph theory.

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N,N-bis(5-methyl-2 hydroxybenzyl)methylamine (MMD)

1H NMR

Figure 6. ¹H-¹H NOESY spectra of (a) MMD; (b) Ce(III)-MMD complex in CDCl₃. - See more at: http://www.mdpi.com/1422-0067/12/7/4365/htm#sthash.ExEZ0GaQ.dpuf

NOESY..........http://www.mdpi.com/1422-0067/12/7/4365/htm

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Figure 6. ¹H-¹H NOESY spectra of (a) MMD; (b) Ce(III)-MMD complex in CDCl₃. - See more at: http://www.mdpi.com/1422-0067/12/7/4365/htm#sthash.ExEZ0GaQ.dpuf

Wednesday, 7 January 2015

Epelsiban

Epelsiban

557296
GSK-557296
GSK-557296-B

(3R,6R)-3-(2,3-Dihydro-1H-inden-2-yl)-1-[(1R)-1-(2,6-dimethyl-3-pyridinyl)-2-(4-morpholinyl)-2-oxoethyl]-6-[(1S)-1-methylpropyl]-2,5-piperazinedione

see..............http://newdrugapprovals.org/2015/01/04/epelsiban-being-developed-by-glaxosmithkline-for-the-treatment-of-premature-ejaculation-in-men/

PAPER

J. Med. Chem., 2012, 55 (2), pp 783–796

DOI: 10.1021/jm201287w

http://pubs.acs.org/doi/abs/10.1021/jm201287w

(3R,6R)-3-(2,3-Dihydro-1H-inden-2-yl)-1-[(1R)-1-(2,6-dimethyl-3-pyridinyl)-2-(4-morpholinyl)-2-oxoethyl]-6-[(1S)-1-methylpropyl]-2,5-piperazinedione (69 EPELSIBAN)

A ………………………. gave colorless needles (75%)

mp 140 °C.

1H NMR (CDCl3) δ 7.49 (d, J =7.8 Hz, 1H, pyridyl-4H),

7.26–7.15 (m, 4H, indanyl-arylH),

7.10 (d, J =8.1 Hz, 1H, pyridyl-5H),

6.68 (s, 1H, NCHpyridyl),

6.49 (d, J = 2.8 Hz, 1H, lactam-NH),

4.10 (dd, J = 10.1 Hz, 4.0 Hz, 1H, NCHindanyl),

4.01 (d, J = 4.5 Hz, NCHsec-butyl),

3.75–2.71 (m, 13H, 8× morpholinyl-H, indanyl-3H, -1H, -2H),

2.62 and 2.58 (2s, 6H, pyridyl-2Me,-6Me),

1.64–1.52 (m, 1H, CHHMe),

0.98–0.79 (m, 2H, CHHMe, CHMeCH2),

0.70 (t, J = 7.1 Hz, 3H, CH2Me),

0.45 (d, J = 6.8 Hz, 3H, CHMe).

LCMS m/z 519 (MH+) single component, gradient 2 (tR 2.70 min).

HRMS calcd for C30H38N4O4(MH+) 519.29658, found 519.29667.

HPLC: 100% (tR 10.388 min).

benzenesulfonic acid;(3R,6R)-6-[(2S)-butan-2-yl]-3-(2,3-dihydro-1H-inden-2-yl)-1-[(1R)-1-(2,6-dimethylpyridin-3-yl)-2-morpholin-4-yl-2-oxoethyl]piperazine-2,5-dione,CAS 1159097-48-9

UNII-H629P9T4UN, GSK557296B, Epelsiban besylate (USAN), Epelsiban besylate [USAN], 1159097-48-9, H629P9T4UN

EPELSIBAN BESYLATE SALT

To a ……………………………….give the besylate (3.214 g, 92.6%) as white crystals of 69B

mp 179–183 °C.

1H NMR (CD3OD) δ 8.30 (d, 1H, J = 8.1 Hz, pyridyl-4H),

7.84–7.80 (m, 2H, PhSO3– 2× ortho-H),

7.78 (d, J = 8.3 Hz, 1H, pyridyl-5H),

7.45–7.38 (m, 3H, PhSO3– 2×meta-H, para-H),

7.23–7.09 (m, 4H, indanyl-arylH),

6.08 (broad s, 1H, NCHpyridyl),

4.00 (d, J =4.6 Hz, 1H, NCHsec-butyl),

3.92 (d, J = 9.9 Hz, 1H, NCHindanyl),

3.78–3.39 and 3.14–2.80 (m, 13H, 8× morpholinyl-H, indanyl-3H, -1H, -2H)),

2.79 and 2.78 (2s, 6H, pyridyl-2Me, -6Me),

1.85–1.74 (m, 1H, CHHMe),

1.59–1.48 (m, 1H, CHHMe),

1.15–1.01 (m, 1H, CHMeCH2),

0.92 (d, J =6.3 Hz, 3H, CHMe),

0.85 (t, J = 7.3 Hz, 3H, CH2Me).

LCMS m/z 519 MH+ single components, tR2.72 min;

circular dichroism (CH3CN) λmax 225.4 nm, dE −15.70, E15086; λmax 276 nm, dE 3.82, E5172.

HRMS calcd for C30H38N4O4 (MH+) 519.2971, found 519.2972.

Anal. (C30H38N4O4·C6H6O3S·3.0H2O) C, H, N, S.

see..............http://newdrugapprovals.org/2015/01/04/epelsiban-being-developed-by-glaxosmithkline-for-the-treatment-of-premature-ejaculation-in-men/

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CARIPRAZINE

CAS 839712-12-8 (free base)

CAS 1083076-69-0…HYDROCLORIDE SALT

trans-N-[4-[2-[4-(2,3-Dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-N’,N’-dimethylurea

Trans-1-{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3- dimethyl-urea

trans-4-{2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexylamine

trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl-urea,

3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea

IN PHASE 3 FOR MAJOR DEPRESSION

see................http://newdrugapprovals.org/2015/01/07/cariprazine-for-major-depressive-disorder/

Journal of Medicinal Chemistry, 2013 , vol. 56, 22 pg. 9199 – 9221

http://pubs.acs.org/doi/abs/10.1021/jm401318w

Biased agonism offers an opportunity for the medicinal chemist to discover pathway-selective ligands for GPCRs. A number of studies have suggested that biased agonism at the dopamine D2 receptor (D2R) may be advantageous for the treatment of neuropsychiatric disorders, including schizophrenia. As such, it is of great importance to gain insight into the SAR of biased agonism at this receptor. We have generated SAR based on a novel D2R partial agonist,tert-butyl (trans-4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)carbamate (4).

This ligand shares structural similarity to cariprazine (2), a drug awaiting FDA approval for the treatment of schizophrenia, yet displays a distinct bias toward two different signaling end points. We synthesized a number of derivatives of 4 with subtle structural modifications, including incorporation of cariprazine fragments. By combining pharmacological profiling with analytical methodology to identify and to quantify bias, we have demonstrated that efficacy and biased agonism can be finely tuned by minor structural modifications to the head group containing the tertiary amine, a tail group that extends away from this moiety, and the orientation and length of a spacer region between these two moieties.

3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (2).

(ref…………Ágai-Csongor, É.; Domány, G.; Nógrádi, K.; Galambos, J.; Vágó, I.; Keserű, G. M.; Greiner, I.; Laszlovszky, I.; Gere, A.; Schmidt, É.; Kiss, B.; Vastag, M.; Tihanyi, K.; Sághy,K.; Laszy, J.; Gyertyán, I.; Zájer-Balázs, M.; Gémesi, L.; Kapás, M.; Szombathelyi,Z.Discovery of cariprazine (RGH-188): A novel antipsychotic acting on dopamine D3/D2receptors Bioorg. Med. Chem. Lett. 2012, 22, 3437– 3440)

Using 50 (40 mg, 112 μmol) as the amine, following general procedure F the product was eluted (CHCl3/CH3OH, 20:1 to 10:1) to give the title compound as a white solid (27 mg, 56%).

mp: 208–209 °C.

1H NMR

δ 7.18–7.10 (m, 2H), 6.99–6.92 (m, 1H), 4.12 (d, J = 7.5 Hz, 1H), 3.64–3.49 (m, 1H), 3.07 (br s, 4H), 2.88 (s, 6H), 2.63 (br s, 4H), 2.50–2.39 (m, 2H), 2.07–1.94 (m, 2H), 1.82–1.72 (m, 2H), 1.52–1.37 (m, 2H), 1.31–1.18 (m, 1H), 1.18–0.99 (m, 4H).

13C NMR

δ 157.8 (C), 151.3 (C), 134.0 (C), 127.5 (C), 127.4 (CH), 124.5 (CH), 118.6 (CH), 56.7 (CH2), 53.4 (CH2), 51.3 (CH2), 49.8 (CH), 36.1 (CH3), 35.7 (CH), 34.0 (CH2), 33.9 (CH2), 32.1 (CH2).

HPLCtR = 8.60 min, >99% purity.

HRMS (m/z): [MH]+ calcd for C21H32Cl2N4O, 427.2026; found, 427.2022.

synthesis

see................http://newdrugapprovals.org/2015/01/07/cariprazine-for-major-depressive-disorder/

see................http://newdrugapprovals.org/2015/01/07/cariprazine-for-major-depressive-disorder/

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Me

DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai), INDIA, worlddrugtracker, 29Yrs Exp. in the field of Organic Chemistry,Working for GLENMARK PHARMA at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational content...........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. सुकून उतना ही देना प्रभू, जितने से जिंदगी चल जाये। औकात बस इतनी देना,कि औरों का भला हो जाये।

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Thursday, 8 January 2015

2-Trimethylammonio-6-hydroxy-benzaldehyde oxime chloride

amcrasto@gmail.com

1-pentyne

amcrasto@gmail.com

A graph theory approach to structure solution of network materials from two-dimensional solid-state NMR data

A graph theory approach to structure solution of network materials from two-dimensional solid-state NMR data

amcrasto@gmail.com

N,N-bis(5-methyl-2 hydroxybenzyl)methylamine (MMD)

amcrasto@gmail.com

Wednesday, 7 January 2015

Epelsiban

amcrasto@gmail.com

CARIPRAZINE

amcrasto@gmail.com

Organic Chemistry Select

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