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

Tuesday, 15 October 2019

Catalyst- and additive-free Baeyer–Villiger-type oxidation of α-iodocyclopentenones to α-pyrones: using air as the oxidant

Graphical abstract: Catalyst- and additive-free Baeyer–Villiger-type oxidation of α-iodocyclopentenones to α-pyrones: using air as the oxidant
An efficient synthetic approach for the synthesis of α-pyrones via Baeyer–Villiger-type oxidation of α-iodocyclopentenones through a catalyst- and additive-free system using air as an environmentally benign oxidant is described. The reaction exhibits excellent functional group compatibility and provides a simple and efficient protocol for the construction of highly functionalized α-pyrones under mild reaction conditions.

Catalyst- and additive-free Baeyer–Villiger-type oxidation of α-iodocyclopentenones to α-pyrones: using air as the oxidant

 Author affiliations
http://www.rsc.org/suppdata/c9/gc/c9gc02725d/c9gc02725d1.pdf

Tuesday, 10 September 2019

Ethyl 4-(4-cyclopropyl-2-oxo-2H-pyran-6-yl)butanoate

Catalyst- and Additive-Free Baeyer−Villiger-type Oxidation of α-Iodocyclopentenones to α-Pyrones: Using Air as the Oxidant

Abstract

An efficient synthetic approach for the synthesis of α-pyrones via Baeyer−Villiger-type oxidation of α-iodocyclopentenones through a catalyst- and additive-free system using air as an environmentally benign oxidant is described. The reaction exhibits excellent functional group compatibility and provides a simple and efficient protocol for the construction of highly functionalized α-pyrones under mild reaction conditions.
Ethyl 4-(4-cyclopropyl-2-oxo-2H-pyran-6-yl)butanoate (2aa) Product 2aa was obtained as yellow oil in 50% yield (38 mg) following the general procedure; 1H NMR (600 MHz, CDCl3) δ 5.84 (s, 1H), 5.61 (s, 1H), 4.13-4.09 (m, 2H), 2.48 (t, J = 7.3 Hz, 2H), 2.33 (td, J = 7.3, 2.3 Hz, 2H), 1.97-1.94 (m, 2H), 1.66-1.63 (m, 1H), 1.26-1.22 (m, 3H), 1.07-1.05 (m, 2H), 0.80-0.79 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 172.8, 163.9, 163.0, 162.8, 106.7, 102.1, 60.5, 33.2, 33.0, 22.1, 15.4, 14.2, 10.0; HRMS (ESI) calcd. for C14H18O4Na [M+Na]+ : 273.1097, found: 273.1101

str1 str2
////////////
https://pubs.rsc.org/en/Content/ArticleLanding/2019/GC/C9GC02725D?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Thursday, 5 September 2019

4-(trifluoromethoxy)benzyl trichloroacetimidate:

4-(Trifluoromethoxy)benzyl Trichloroacetimidate





To a stirred suspension of NaH (60%, 127 mg, 3.45 mmol) in t-BuOMe (100 mL) was added 4-(trifluoromethoxy)benzyl alcohol 11 (5 mL, 34.5 mmol) dropwise by syringe at room temperature. After H2 evolution had ceased (about 5 min), the clear mixture was cooled to 0 °C. Cl3CCN (3.46 mL, 34.5 mmol) was added dropwise by syringe, and the resulting solution was stirred for 1 h. After warming to room temperature, the solution was concentrated in vacuo, and the residue was resuspended in heptane (100 mL) containing MeOH (0.14 mL, 3.45 mmol). After 10 min of stirring, the suspension was filtered through a thin bed of silica and washed with heptane. Concentration in vacuo affords the title compound as a yellow-orange liquid (11.4 g, 98%) that was used directly without further purification. Rf 0.3 (5% EtOAc/hexanes);


 1H NMR (501 MHz, CDCl3) δ 8.43 (s, 1H), 7.48 (d, J = 8.2 Hz, 2H), 7.24 (d, J = 8.2 Hz, 2H), 5.35 (s, 2H); 


13C NMR (126 MHz, CDCl3) δ 162.6, 149.3, 134.3, 129.4, 121.6, 121.3, 119.6, 69.9; 

IR [CH2Cl2 solution] νmax (cm−1) 3345, 2954, 1667, 1511, 1261, 1221, 1166, 1077, 998, 828, 797, 649; 


HRMS (ESI-TOF) calcd for C10H7Cl3F3NO2 334.95, found C8H6F3O 174.03.

(R)-3-Chloro-2-hydroxypropyl-4-methoxybenzoate



(R)-3-Chloro-2-hydroxypropyl-4-methoxybenzoate 10

To a stirred solution of (R)-3-chloro-1,2-propanediol (6.61 g, 59.8 mmol) in CH2Cl2 (120 mL) was added imidazole (4.07 g, 59.8 mmol). After the reaction mixture had cooled to 0 °C, p-methoxybenzoyl chloride (10.2 g, 59.8 mmol) in CH2Cl2 (10 mL) was added dropwise via addition funnel. The resulting solution was allowed to warm to room temperature and stirred until complete consumption of starting material by thin layer chromatography (TLC). The mixture was poured into saturated aq NH4Cl (150 mL), and the aqueous layer was extracted with CH2Cl2 (3 × 100 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo to provide chlorohydrin 10as a clear, viscous oil (11.43 g, 78%) that was used without further purification. Rf 0.3 (20% EtOAc/hexanes); ee >99% as determined by chiral SFC (see the Supporting Information); 


1H NMR (500 MHz, CDCl3) δ 8.07−7.94 (m, 2H), 7.00−6.88 (m, 2H), 4.46 (d, J = 5.1 Hz, 2H), 4.22 (dd, J = 10.6, 5.3 Hz, 1H), 3.88 (s, 3H), 3.78−3.64 (m, 2H), 2.73 (d, J = 5.6 Hz, 1H); 


13C NMR (126 MHz, CDCl3) δ 166.7, 163.9, 132.1, 121.9, 114.0, 70.1, 65.7, 55.7, 46.3; 

IR [CH2Cl2 solution] νmax (cm−1) 3454, 2959, 2889, 1713, 1606, 1512, 1259, 1170, 1104, 1028, 848, 770, 697, 614; 

HRMS (ESI-TOF) calcd for C11H13ClO4 (M)+244.0573, found 244.0501.

https://pubs.acs.org/doi/full/10.1021/jo1015807
/////////////////
https://pubs.acs.org/doi/suppl/10.1021/jo1015807/suppl_file/jo1015807_si_001.pdf

Wednesday, 4 September 2019

Pretomanid

Pretomanid.svg
Pretomanid

read syn  https://newdrugapprovals.org/2019/09/04/pretomanid-%e3%83%97%e3%83%ac%e3%83%88%e3%83%9e%e3%83%8b%e3%83%89/

The combined organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated. Chromatography (75% EtOAc/hexanes) followed by recrystallization (i-PrOH/hexanes) affords PA-824 (1) (2.41 g, 62%) as a crystalline solid. Mp 150−151 °C (lit.(11a) mp 149−150); Rf 0.2 (75% EtOAc/hexanes); ee >99.9% as determined by chiral SFC (see the Supporting Information);
 1H NMR (500 MHz, d6-DMSO) δ 8.09 (s, 1H), 7.48 (d, J = 8.6 Hz, 2H), 7.39 (d, J = 8.2 Hz, 2H), 4.81−4.62 (m, 3H), 4.51 (d, J = 11.9 Hz, 1H), 4.39−4.19 (m, 3H);
 13C NMR (126 MHz, d6-DMSO) δ 148.7, 148.1, 143.0, 138.3, 130.4, 122.0, 120.0, 119.8, 69.7, 68.8, 67.51, 47.73;
IR [CH2Cl2 solution] νmax (cm−1) 2877, 1580, 1543, 1509, 1475, 1404, 1380, 1342, 1281, 1221, 1162, 1116, 1053, 991, 904, 831, 740;
HRMS (ESI-TOF) calcd for C14H12F3N3O5 359.0729, found 359.0728.





Tuesday, 6 August 2019

Verubecestat Impurity 10

Verubecestat.svg

Verubecestat



str1
Verubecestat Impurity 10
1H NMR (600 MHz, Acetonitrile-d3) δ 9.86 (s, 1H), 8.21 (d, J = 3.0 Hz, 1H), 8.02 (dd, J = 7.5, 2.8 Hz, 1H), 7.96 (d, J = 8.9 Hz, 1H), 7.81 (ddd, J = 8.7, 4.2, 2.7 Hz, 1H), 7.24 (dd, J = 8.9, 3.0 Hz, 1H), 7.19 (d, J = 8.7 Hz, 2H), 7.07 (dd, J = 12.0, 8.7 Hz, 1H), 6.88 (d, J = 8.7 Hz, 2H), 4.06 (d, J = 14.6 Hz, 1H), 3.92 (d, J = 14.6 Hz, 1H), 3.81 (d, J = 14.2 Hz, 1H), 3.75 (s, 3H), 3.65 (ddd, J = 11.7, 9.8, 3.9 Hz, 1H), 3.39 (d, J = 14.3 Hz, 1H), 2.86 (s, 3H), 2.59 (td, J = 10.3, 4.0 Hz, 1H), 2.55 (s, 3H), 2.28 (s, 3H), 2.22 – 2.09 (m, 1H), 1.78 – 1.71 (m, 2H), 1.69 – 1.64 (m, 1H), 1.61 – 1.54 (m, 4H), 1.41 (qt, J = 13.7, 3.9 Hz, 1H), 1.28 (qt, J = 13.3, 3.8 Hz, 1H), 1.17 – 1.07 (m, 1H).
13C NMR (151 MHz, Acetonitrile-d3) δ 163.79, 160.26, 156.68, 149.74, 137.95, 136.00 (d, J = 2.3Hz), 134.69 (d, J = 13.7 Hz), 134.15, 130.58, 129.35, 123.67, 120.82 (d, J = 8.7 Hz), 120.51 (d, J = 4.3 Hz), 119.60, 116.85, 114.82, 63.09, 60.77, 60.31 (d, J = 5.5 Hz), 55.84, 54.27 (d, J = 3.4 Hz), 53.30, 34.11, 33.75, 31.85, 30.96, 30.23 (d, J = 3.3 Hz), 28.91, 26.13, 25.25.
19F NMR (564 MHz, Acetonitrile-d3) δ -119.08. HRMS [M+H] (C32H43FN6O4S) calc. 627.3123, obs. 627.3151.

Improved Process for a Copper-Catalyzed C–N Coupling in the Synthesis of Verubecestat
Eric M. Phillips*
Cite This:Org. Process Res. Dev.2019XXXXXXXXXX-XXX
Publication Date:July 23, 2019
 
https://doi.org/10.1021/acs.oprd.9b00192
Verubecestat is a β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor which was previously evaluated for the treatment of Alzheimer’s disease. The synthesis of verubecestat relies on a Cu-catalyzed carbon–nitrogen coupling. During process development, observations of impurity formation led to a more robust understanding of the catalyst. The transformation was discovered to be highly dependent on the ratio of ligand to substrate concentration during the course of the reaction. In-depth studies aimed at attaining mechanistic understanding provided an explanation of experimental findings and ultimately led to the identification of conditions that resulted in a more robust process.

///////////Verubecestat,  Impurity 10

Monday, 8 April 2019

AB 680 « New Drug Approvals

AB 680 « New Drug Approvals: AB 680 C20H24ClFN4O9P2, 580.827 g/mol Cas 2105904-82-1 1H-Pyrazolo[3,4-b]pyridin-4-amine, 6-chloro-N-[(1S)-1-(2-fluorophenyl)ethyl]-1-[5-O-[hydroxy(phosphonomethyl)phosphinyl]-β-D-ribofuranosyl]- […

Wednesday, 27 March 2019

Taselisib

Taselisib skeletal.svg
TASELISIB

SYNTHESIS........https://newdrugapprovals.org/2018/06/15/rg-7604taselisib/

CLIP

Manufacture of the PI3K β-Sparing Inhibitor Taselisib. Part 2: Development of a Highly Efficient and Regioselective Late-Stage Process

 Department of Small Molecule Process ChemistryGenentech Inc.1 DNA Way, South San Francisco, California 94080, United States
 Small Molecules Technical Development PTDC-CF. Hoffmann-La Roche Ltd.Grenzacherstrasse 124, 4070 Basel, Switzerland
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.9b00050
*E-mail: stjean.frederic@gene.com. (F.St.-J.), *E-mail: angelaud.remy@gene.com. (R.A.)
Abstract Image
A highly efficient and regioselective manufacturing route for the phosphoinositide 3-kinase β-sparing inhibitor taselisib was developed. Highlights of the synthesis include: (1) magnesium-mediated formation of a challenging cyclic amidine; (2) regioselective imidazole construction via alkylation/condensation with bromopyruvic acid; and (3) triazole formation with 2-isopropyl acetamidrazone to generate the key bromobenzoxazepine core intermediate. Subsequent highly efficient one-pot palladium-catalyzed Miyaura borylation/Suzuki cross-coupling/saponification, followed by a 1,1′-carbonyldiimidazole-mediated coupling with ammonia, led to the pentacyclic taselisib. This new synthetic approach provides a more efficient route to taselisib with a significant decrease in process mass intensity compared to the previous early development routes to the bromobenzoxazepine core. Finally, implementation of a controlled crystallization provided the active pharmaceutical ingredient with the desired polymorphic form.
Taselisib was obtained in 90% yield (16.2 kg) as a white to off-white solid (>99.9 wt %; >99.9 A%) as Form B crystal.
mp (DSC): 257–258 °C.
HRMS (ESI-CID) m/z Calcd for [M + H]+ C24H29N8O2: 461.2408; found: 461.2409.
 1H NMR (600 MHz, DMSO-d6) δ ppm 8.41 (s, 1H), 8.37 (d, J = 8.4, 1H), 8.02 (s, 1H), 7.88 (m, 1H), 7.45 (dd, J = 8.4, 1.7 Hz, 1H), 7.36 (d, J = 1.7 Hz, 1H), 7.20 (br s, 1H), 6.84 (br s, 1 H), 5.83 (sept, J = 6.6 Hz, 1H), 4.53–4.51 (m, 2H), 4.52 (m, 2H), 2.26 (s, 3H), 1.75 (s, 6H), 1.47 (d, J = 6.7 Hz, 6H).
 13C NMR (DMSO-d6, 151 MHz) δ = 173.8, 158.3, 155.9, 147.3, 144.0, 136.6, 134.6, 130.3, 129.9, 126.4, 123.6, 120.4, 119.3, 116.2, 115.3, 68.3, 64.5, 49.9, 49.7, 25.5, 25.5, 22.3, 22.3, 13.8.
Ultraviolet/Visible Spectroscopy
Apparatus: Perkin Elmer, UV-6190, Lambda 25
Solvent: Acetonitrile/Water 1:1 (v/v)



str1 str2 str3

////////////////

“ALL FOR DRUGS” 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

READ

ANTHONY MELVIN CRASTO
NDA
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO …..FOR BLOG HOME CLICK HERE
 
Join me on Linkedin

View Anthony Melvin Crasto Ph.D's profile on LinkedIn

Join me on Facebook FACEBOOK
Join me on twitterFollow amcrasto on Twitter
Join me on google plus Googleplus

 amcrasto@gmail.com

CALL +919323115463  INDIA
//////////////

1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic pivalic anhydride

str1 str2
1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic pivalic anhydride (10): tan solid,
mp (DSC): onset = 172.4 °C, peak temperature = 173.0 °C;

1H NMR (400 MHz, CD3CN) δ 8.23 (d, J = 7.6 Hz, 1 H), 7.35–7.25 (m, 4 H), 6.36 (d, J = 8.0 Hz, 1 H), 2.02 (s, 3 H), 1.25 (s, 9 H);
13C NMR (100 MHz, CD3CN) 175.9 (1 C), 163.6 (d, 1 C, JCF = 245.4 Hz), 162.9 (1 C ), 161.1 (1 C), 158.2 (1 C), 148.6 (1 C), 135.7 (1 C), 131.0 (d, JCF = 8.7 Hz, 2 C), 117.7 (d, JCF = 23.2 Hz, 2 C), 116.0 (1 C), 107.1 (1 C), 40.4 (1 C), 27.0 (3 C), 22.8 (1 C);
19F NMR (376 MHz, CD3CN) δ -114.2 (m, 1 F);
IR (ATR, cm-1 ) 2966 (w), 2939 (w), 2876 (w), 1789 (vs), 1697 (s), 1682 (vs), 1554 (s), 1509 (vs);
HRMS calcd for C18H18O4NFNa (M+Na+ ) = 354.1112; found 354.1113, δ = 0.3 ppm.



“ALL FOR DRUGS” 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

READ

ANTHONY MELVIN CRASTO
NDA
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO …..FOR BLOG HOME CLICK HERE
 
Join me on Linkedin

View Anthony Melvin Crasto Ph.D's profile on LinkedIn

Join me on Facebook FACEBOOK
Join me on twitterFollow amcrasto on Twitter
Join me on google plus Googleplus

 amcrasto@gmail.com

CALL +919323115463  INDIA
//////////////

Thursday, 31 January 2019

Telescoped Sequence of Exothermic and Endothermic Reactions in Multistep Flow Synthesis


Abstract Image
A multistep sequential flow synthesis of isopropyl phenol is demonstrated, involving 4-step exothermic, endothermic, and temperature sensitive reactions such as nitration, reduction, diazotization, and high temperature hydrolysis. Nitration of cumene with fuming nitric acid produces 2- and 4-nitrocumene which are converted into respective cumidines by the hydrogenation using Pd/Ni catalyst in H-cube with gravity separation. Hydrolysis of in situ generated diazonium salts in the boiling acidic conditions is carried out using integration of flow and microwave-assisted synthesis. 58% of 4-isopropyl phenol was obtained. The sequential flow synthesis can be applied to synthesize other organic compounds involving this specific sequence of reactions.

Telescoped Sequence of Exothermic and Endothermic Reactions in Multistep Flow Synthesis

Chemical Engineering & Process Development DivisionCSIR-National Chemical LaboratoryDr. Homi Bhabha Road, Pune 411008, India
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.8b00008
STR1
 
*Phone: +91-20-25902153, E-mail: aa.kulkarni@ncl.res.in.
 
STR1 STR2
Amol A. Kulkarni
Dr.Amol A. Kulkarni
Chemical Engineering & Process Development
CSIR-National Chemical Laboratory
logo
Dr. Amol A. Kulkarni is a Scientist in the Chemical Engineering Division at the National Chemical Laboratory. He did his B. Chem. Eng. (1998), M. Chem. Eng (2000) and Ph.D. in chemical engineering (2003) all from the University Dept. of Chem. Technology (UDCT, Mumbai). In 2004 he worked at the Max Planck Institute-Magdeburg (Germany) as a Alexander von Humboldt Research Fellow. At NCL he is driving a research program on the design of microreactors and exploring their applications for continuous syntheses including of nanoparticles. He has been awarded with the Max-Planck-Visiting Fellowship from the Max-Planck-Society, Munich for 2008-2011. His research areas include: (i) design and applications of microreactors, (ii) design of multiphase reactors, (iii) experimental and computational fluid dynamics, and (iv) nonlinear dynamics of coupled systems. He is an active member of Initiative for Research and Innovation in Science (IRIS) supported by Intel’s Education Initiative to organize National Science Fair and popularize science in India.

Image result for Yachita Sharma ncl pune

Yachita Sharma
Location Pune, India
Yachita Sharma is a PhD student at CSIR-National Chemical Laboratory, Pune (India). She received her MSc in Applied Organic Chemistry in 2010. Her work focuses on exploring the continuous flow synthesis involving exothermic reactions and their integration.
 
Image result for Yachita Sharma ncl pune
Arun Nikam
Location, Pune, India
Email: arun11nikam@gmail.com
Arun was born and raised in Koregaon, Maharashtra, India. He completed his bachelors and masters in chemical sciences from Shivaji Unversity, Kolhapur, India. Currently, He is pursuing his Ph. D. under the supervision of Dr. Amol A. Kulkarni and Dr. B. L. V. Prasad. His work mainly focuses on flow synthesis of nanoparticles, drug formulation, and polymers. He develops new synthesis procedures and translates into flow chemistry to increase productivity with excellent control over the quality of the product. He is also exploring the application of nanoparticles in catalysis, electronics and pharmaceutical fields. He specializes in microwave-assisted continuous flow synthesis of nanomaterial and organic intermediate. Apart from his research, he actively pursues Yoga and spirituality. He also likes to play volleyball and has competed in inter CSIR tournaments.

/////////isopropyl phenol, flow chem,

“ALL FOR DRUGS” 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

READ

ANTHONY MELVIN CRASTO
NDA
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO …..FOR BLOG HOME CLICK HERE
 
Join me on Linkedin

View Anthony Melvin Crasto Ph.D's profile on LinkedIn

Join me on Facebook FACEBOOK
Join me on twitterFollow amcrasto on Twitter
Join me on google plus Googleplus

 amcrasto@gmail.com

CALL +919323115463  INDIA
//////////////