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.
 


.

 


 

 

 

 
 
 

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