(Z)-methyl 3-(2-oxopyrrolidin-1-yl-3-phenylacrylate

(Z)-methyl 3-(2-oxopyrrolidin-l-vO-3-phenylacrylate (3a )

Ή NMR (400 MHz, CDC1₃) δ 7.47-7.38 (m, 5H), 6.27 (s, 1H), 3.75 (s, 3H), 3.55 (t, J = 7.0 Hz, 2H), 2.60 (t, J = 8.0 Hz, 2H), 2.22-2.15 (m, 2H);  



¹³C NMR (100 MHz, CDC1₃) δ 175.35, 165.02, 148.23, 134.75, 130.60, 128.95, 127.06, 1 14.46, 51.59, 49.12, 31.68, 19.18;


HRMS (ESI) m/z [M+H]+: Calcd for Ci₄H,₆N0₃: 246.1 130 Found: 246.1 139.










(Z)methyl 3-(4-methoxyphenyl)-3- -oxopyrrolidin-l -yl acrylate (3 b)

Ή NMR (400 MHz, CDC1₃) δ 7.41 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 6.21 (s, 1H), 3.84 (s, 3H), 3.74 (s, 3H), 3.56 (t, J = 7.0 Hz, 2H), 2.60 (t, J = 8.0 Hz, 2H), 2.23-2.15 (m, 2H);  


^,3C NMR (100 MHz, CDC1₃) δ 175.44, 165.13, 161.68, 148.32, 128.56, 126.94, 1 14.38, 1 12.38, 55.42, 51.46, 49.26, 31.72, 19.21 ;


HRMS (ESI) m/z [M+H]+: Calcd for Ci₅H,₈N0₄: 276.1236 Found: 276.1239.







http://www.google.com/patents/WO2012173572A1?cl=en

TAKE A FREE TOUR

Cape Point. SOUTH AFRICA





















.....


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

Join me on Linkedin

Join me on Facebook FACEBOOK

Join me on twitter     

Join me on google plus Googleplus

 amcrasto@gmail.com

 

///////////

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

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

 

 
 
 .

 

 

 

 
 
 
 
 

 
 

 

 

 

 

 
 

 


 
 

 










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

4-Amino-3-(4-(dimethylαmino)phenyl)-2-(4-methoxyphenyl)-furo[2,3-d]pyrimidine

Example 2:
4-Amino-3-(4-(dimethylαmino)phenyl)-2-(4-methoxyphenyl)-furo[2,3-d]pyrimidine

Example 2 was prepared according to procedures similar to those shown in Scheme 3. 2(A) 2-Amino-3-cyano-5-(4-methoxyphenyl)furan

To a suspension of α-((4-methoxybenzoyl)methyl)malononitrile (9.66g, 45.1 mmol) in acetic acid (50ml) was added cone, hydrogen chloride (11,3 ml). The mixture was stirred at room temperature for 2 hours, and then poured into water. The resultant precipitation was filtrated, washed with water and ethanol, and dried under reduced pressure to give the Intermediate of Example 2(A) ( 5.54g, 56%) as a solid. 1 H NMR (400MHz, CDCI3) ppm 3.83 (s, 3H), 4.74 (brs, 2H), 6.39 (s, 1 H), 6.90 (m, 2H), 7.42 (m, 2H).
2(B) 4-Amino-2-(4-methoxyphenyl)furo[2,3-d]pyrimidine (Example 14)

A solution of the Intermediate of Example 2(A) ( 5.54g, 25.9mmol) in formamide (100ml) was heated at 200°C for 1 hour. The mixture was cooled with an ice bath, and then poured into cold water. The precipitated material was filtrated, washed with water and ethanol, and dried under reduced pressure to give the Intermediate of Example 2(B) (5.61 g, 69<y₀) as a solid. 1 H NMR (400MHz, CDCI3) ppm 3.87 (s, 3H), 5.14 (s, 2H), 6.72 (s, 1 H), 6.99 (m, 1 H), 7.78 (m, 2H), 8.38 (s, 1 H). LC/MS: m/z 242 (M+l)⁺;
2(C) 4-Amino-3-bromo-2-(4-methoxyphenyl)furo[2,3-d]pyrimidine (Example 33)

To a suspension of the Intermediate of Example 2(B) (4.02g, 16.7mmol) in carbon tetrachloride (100ml), NBS (3.42g, 19.2mmol) was added. The mixture was refluxed for 4 hours, and then concentrated in vacuo. The residual material was suspended in ethanol, refluxed for 20 minutes, and cooled to 0°C. The precipitated material was filtrated, washed with ethanol, and dried under reduced pressure to afford the Intermediate of Example 2(C) (4.71g, 88%). 1 H NMR (400MHz, DMSO-d6) ppm 3.84 (s, 3H), 7.13 (m, 2H), 7.95 (m, 2H), 8.24 (s, 1 H). LC/MS: m/z 320 (M)⁺, 322 (M+2)⁺.
2(D) 4-Amino-3-(4-(dimethylamino)phenyl)-2-(4-methoxyphenyl)furo[2,3- d]pyrimidine

A mixture of the Intermediate of Example 2(C) (62.4 mg, 0.195 mmol), (4- dimethyl amino)phenyl-boronic acid (101 mg, 0.61 mmol), tetrakis(triphenyl phosphine)-palladium(O) (15.5 mg, 0.013 mmol) was suspended in the mixture of DME (2.0 ml), DMF (0.5 ml), and 2M aqueousNa_C03 (1.0 ml) under argon atmosphere. The mixture was refluxed over night, diluted with dichloromethane, and washed with aqueous Na₂CU3. The organic phase was separated, concentrated in vacuo, and purified by chromatography on a silica gel column using hexane / ethyl acetate (3:1- 1 :1) as an eluant to afford the title compound of Example 2 (37 mg) as a solid. 1 H NMR (400MHz, CDCI3) ppm 3.05 (s, 6H), 3.80 (s, 3H), 4.94 (brs, 2H), 6.82 (m, 4H), 7.31 (m, 2H), 7.56 (m, 2H), 8.34 (s, 1 H). LC/MS: m/z 361 (M+1) ⁺.










///////WO2003022852A2

Tweni Beach - SA Venues

www.sa-venues.com › ... › KwaZulu Natal › South Coast › Umtentweni

Tweni Beach in Umtentweni, KwaZulu Natal: A little off the beaten track, Tweni Beach lies just 2km from the popular holiday hub of Port Shepstone. A ... cont.
 


.

 


 

 

 

 
 
 

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