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

Friday 13 November 2015

N-cycIopropyl-2-(4-fluorophenyl)-3-(4-((E)-3-(hydroxyamino)-3-oxoprop- l-en-l-yl)phenyl)acrylamide



Figure imgf000030_0002

N-cycIopropyl-2-(4-fluorophenyl)-3-(4-((E)-3-(hydroxyamino)-3-oxoprop- l-en-l-yl)phenyl)acrylamide



Example 1:
Synthesis of N-cycIopropyl-2-(4-fluorophenyl)-3-(4-((E)-3-(hydroxyamino)-3-oxoprop- l-en-l-yl)phenyl)acrylamide.

Step-I
Preparation of methyl (E)-3-(4-formylphenyl)acrylate

A suspension of (E)-3-(4-formylphenyl)acrylic acid (2 g, 10.5 mmol) in methanol (30 mL) was cooled to 5 ºC and then concentrated H2SO4 (3 niL) was added under stirring and heated at 60 ºC for 2 hours. The solvent was removed by evaporation and the obtained compound was stirred with water (100 mL) for 15 minutes. The precipitated white solid was filtered, washed with water (300 mL) and dried to get the pure product (1.9 g. 86% yield). Step-II Preparation of 2-(4-fluorophenyl)-3-(4-((E)-3-methoxy-3-oxoprop-l-en-l-yl) phenyl)acrylic acid

A mixture of 4-fluorophenylacetic acid (2.5 g, 13.2 mmol) and methyl (E)-3-(4- formylphenyl) acrylate (2.03 g, 13.2 mmol) were dissolved under stirring with acetic anhydride (8 mL). To this mixture, diisopropylethylamine (DIPEA) (3.4 mL, 19.7 mmol) was added and stirred at 30 ºC for 2 hours. Upon completion (as monitored by TLC using 100% ethyl acetate as eluent), the reaction mixture was poured into water and the pH adjusted to 1 using dilute HCl (1 : 1). The aqueous layer was extracted with ethyl acetate (2 x 150 mL). The combined ethyl acetate layer was washed with water till the washings were neutral and dried over anhydrous Na2SC>4. The ethyl acetate layer was evaporated to dryness to obtain a sticky compound and further triturated with cold dichloromethane
(DCM) to furnish a white solid. The solid obtained was filtered and dried under vacuum to afford the title compound (2 g, 47% yield).
Step-III
Preparation of methyl 3-(E) (4-(3-(cyclopropyIamino)-2-(4-fluorophenyl)-3-oxoprop-l- en-l-yl)phenyl)acrylate

A mixture of 2-(4-fluorophenyl)-3-(4-((E)-3-methoxy-3-oxoprop- l -en-l -yl) phenyl)acrylic acid (0.23 g, 0.71 mmol) and cyclopropylamine (0.03 g, 0.60 mmol), EDCl (0.27 g, 1.4 mmol), HOBt (0.10 g, 0.71 mmol) was dissolved in N,N-dimethyiformamide (DMF) (6 mL) under stirring. Triethylamine (TEA) (0.75 mL, 36 mmol) was added dropwise with constant stirring to the above reaction mixture and it was stirred at 30 ºC for 2 hours. Subsequently the reaction mixture was diluted with ethyl acetate and washed successively with water (3 x 50 mL) and brine (3 x 50 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated to afford the pure compound (0.25 g. 96% yield). Step-IV
Preparation of yV-cyclopropyl-2- (4-fluorophenyl)-3-(4-((E)-3-(hydroxyamino)-3- oxoprop-1-en-l-yl) phenyl) acrylamide.

Hydroxylamine hydrochloride (0.86 g, 12.3 mmol) in methanol (3 mL) was mixed with KOH (0.69 g, 12.3 mmol) in methanol (3 mL) at 0 ºC, and sonicated for 2 minutes, the white precipitate formed was filtered. The filtrate was added to methyl 3-(E)(4-(3- (cyclopropylaιnino)-2-(4-fluorophenyl)-3-oxoprop-l -en-l -yl)phenyl)acrylate (0.25 g, 0.68 mmol) in DCM (1.5 mL) and the mixture was stirred at room temperature, for 30 minutes. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (2 x 150 mL). The ethyl acetate layer was dried over anhydrous Na2SO4 and concentrated to obtain a sticky compound, which was triturated with DCM (15 mL). The pale brown solid obtained was filtered and washed with DCM (3 x 5 mL) to afford the title compound (0.07g, 28% yield). 1H NMR (DMSOd6) δ (ppm): 0.49-0.53 (2H, dd, -CH2), 0.61 -0.66 (2H, m, - CH2), 2.72-2.77 (IH, m, -CH), 6.38-6.42 (I H, d, =CH), 7.00-7.02 (2H, d, Ar-H), 7.16-7.27 (5H, m, Ar-H and =CH), 7.33-7.43 (3H, m, Ar-H and =CH), 7.81 -7.82 (I H, d, -NH). 9.04 (I H, s, -OH), 10.73 (IH, s, -NH). MS m/z: 367.1 (M++l).









/////////WO2009053808A2

 Lake Eland Game Reserve, KwaZulu-Natal, South Africa

Lake Eland

www.lakeeland.co.za/
Welcome to Lake Eland Game Reserve, KwaZulu-Natal, South Africa. A perfect venue for a family holiday, romantic getaway or simply a day's outing.

D219 Oribi Flats East, Port Shepstone, 4240, South Africa
+27 39 687 0395

 Map of Lake Eland Game Reserve

 
 
 .

 

 

 

 
 
 
 
 

 
 

 

 

 

 

 
 

 


 
 

 










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

No comments:

Post a Comment