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Friday, 20 March 2020

Favipiravir

ChemSpider 2D Image | favipiravir | C5H4FN3O2
  • Molecular FormulaC5H4FN3O2
  • Average mass157.103 Da
259793-96-9 [RN]
2-Pyrazinecarboxamide, 6-fluoro-3,4-dihydro-3-oxo-
 
6-Fluoro-3-hydroxypyrazine-2-carboxamide
6-Fluoro-3-oxo-3,4-dihydro-2-pyrazinecarboxamide
 
8916
Avigan
ファビピラビル
Favipiravir
SYN

Electronic supplementary material

 
Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1315 kb)



Ref

Drug Discoveries & Therapeutics. 2014; 8(3):117-120.
 mp = 178-180°C. 1 H-NMR (600 MHz, DMSO): δ 12.34 (brs, 1H, OH), 8.31 (d, 1H, pyrazine H, J = 8.0 Hz), 7.44 (s, 1H, CONH2), 5.92 (s, 1H, CONH2). 13C-NMR (75 MHz, DMSO): δ 168.66, 159.69, 153.98, 150.76, 135.68. HRMS (ESI): m/z [M + H]+ calcd for C5H5FN3O2 + : 158.0366; found: 158.0360.

PAPER
Chemical Papers (2017), 71(11), 2153-2158.

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 514 kb)



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Wednesday, 11 March 2020

NIDUFEXOR

Nidufexor Chemical Structure
Nidufexor.png
NIDUFEXOR
LMB763
4-[[benzyl-(8-chloro-1-methyl-4H-chromeno[4,3-c]pyrazole-3-carbonyl)amino]methyl]benzoic acid
Nidufexor is a farnesoid X receptor (FXR) agonist.
Molecular Weight
487.93
Formula
C₂₇H₂₂ClN₃O₄
CAS No.
1773489-72-7
PHASE 2 Treatment of Liver and Biliary Tract Disorders,
Agents for Diabetic Nephropathy, NOVARTIS

1 (7.6 g, 89% yield) as a white solid. Melting point: 232.6 °C.
1 H NMR (400 MHz, DMSO): δ 12.93 (s, 1H), 7.96−7.85 (m, 2H), 7.71 (dd, J = 7.1, 2.5 Hz, 1H), 7.42−7.20 (m, 8H), 7.06 (dd, J = 8.7, 1.9 Hz, 1H), 5.45 (d, J = 3.9 Hz, 2H), 5.25 (d, J = 9.2 Hz, 2H), 4.58 (d, J = 12.1 Hz, 2H), 4.12 (d, J = 16.6 Hz, 3H).
13C NMR (101 MHz, DMSO-d6): δ 167.07, 162.21, 151.98, 142.65, 139.18, 132.20, 132.67, 129.70, 129.50, 129.50, 128.53, 128.53, 127.43, 127.43, 127.43, 127.43, 127.43, 125.53, 122.24, 119.0, 117.09, 116.64, 64.51, 50.68, 48.24. LC-MS m/z: 488.2/490.2 (M +H)+ ; chlorine pattern; method 3; RT = 1.41 min.
Elemental Analysis calcd for C27H22ClN3O4: C 66.46, H 4.54, N 8.61; found: C 66.43, H 4.56, N 8.62.
TRIS Salt Formation. Methanol (400 mL) was added to a mixture of 1 (4.0 g, 8.2 mmol) and 2-amino-2-hydroxymethylpropane-1,3-diol (TRIS, 1.0 g, 8.2 mmol). The mixture was heated to 70 °C for 0.5 h. After cooling to room temperature, the solvent was removed in vacuum. The residue was sonicated in dichloromethane (10 mL) and concentrated again. The resulting white solid was dried under vacuum overnight. The crude material was crystallized by slurring the solid residue in a 4:1 mixture of acetonitrile and methanol (5 mL). The mixture was stirred at room temperature for 24 h to give 4-((N-benzyl-8-chloro-1-methyl-1,4-dihydrochromeno- [4,3-c]pyrazole-3-carboxamido)methyl)benzoic acid TRIS salt as a white salt (3.7 g, 73% yield). Melting point: 195.6 °C. 1 H NMR (400 MHz, DMSO): δ 7.92−7.80 (m, 2H), 7.78−7.64 (m, 1H), 7.41− 7.19 (m, 8H), 7.13−7.00 (m, 1H), 5.44 (s, 2H), 5.25−5.14 (m, 2H), 4.61−4.48 (m, 2H), 4.18−4.03 (m, 3H), 3.39 (s, 7H). TRIS OH masked by water peak. LC-MS m/z: 488.0/490.0 (M+H)+ ; chlorine pattern, method 3. RT = 1.58 min. Elemental Analysis calc for C31H33ClN4O7: C 61.00, H 5.36, N 9.15; found: C 60.84, H 5.34, N 9.13.


Patent
WO 2015069666
///////NIDUFEXOR, LMB 763, Phase II, PHASE 2, Liver and Biliary Tract Disorders,  Diabetic Nephropathy, NOVARTIS
CN1C(C2=CC(Cl)=CC=C2OC3)=C3C(C(N(CC4=CC=CC=C4)CC5=CC=C(C(O)=O)C=C5)=O)=N1

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
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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
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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.