e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

Tetrahedron letters

Regioselective cross-coupling reactions and nucleophilic aromatic substitutions on a 5, 7-dichloropyrido [4, 3-d] pyrimidine scaffold

MY Jang, S De Jonghe, LJ Gao, P Herdewijn

Index: Jang, Mi-Yeon; Jonghe, Steven De; Gao, Ling-Jie; Herdewijn, Piet Tetrahedron Letters, 2006 , vol. 47, # 50 p. 8917 - 8920

Full Text: HTML

Citation Number: 14

Abstract

The synthesis of a 5, 7-dichloropyrido [4, 3-d] pyrimidine scaffold is described. The chlorine at position 5 can selectively be displaced by different palladium-catalyzed cross-coupling reactions and nucleophilic aromatic substitutions. In the subsequent step, the chlorine at position 7 can be further derivatized. The described synthetic sequence allows for the construction of a diverse pyrido [4, 3-d] pyrimidine library with structural variations at ...

2,6-Dichloro-4-({[(2-methyl-2-propanyl)oxy]carbonyl}amino)nicotinic acid Structure

2,6-Dichloro-4-...

~%

4-AMINO-2,6-DICHLORONICOTINAMIDE Structure

4-AMINO-2,6-DIC...

tert-Butyl (2,6-dichloropyridin-4-yl)carbamate Structure

tert-Butyl (2,6...

~%

4-AMINO-2,6-DICHLORONICOTINAMIDE Structure

4-AMINO-2,6-DIC...

4-AMINO-2,6-DICHLORONICOTINIC ACID Structure

4-AMINO-2,6-DIC...

~%

4-AMINO-2,6-DICHLORONICOTINAMIDE Structure

4-AMINO-2,6-DIC...

2,6-dichloropyridin-4-amine Structure

2,6-dichloropyr...

~%

4-AMINO-2,6-DICHLORONICOTINAMIDE Structure

4-AMINO-2,6-DIC...

morpholine Structure

5,7-Dichloropyrido[4,3-d]pyrimidin-4(1H)-one Structure

5,7-Dichloropyr...

~%

7-chloro-5-morpholin-4-yl-1H-pyrido[4,3-d]pyrimidin-4-one Structure

7-chloro-5-morp...

4-AMINO-2,6-DICHLORONICOTINIC ACID Structure

4-AMINO-2,6-DIC...

~%

7-chloro-5-morpholin-4-yl-1H-pyrido[4,3-d]pyrimidin-4-one Structure

7-chloro-5-morp...

4-AMINO-2,6-DICHLORONICOTINAMIDE Structure

4-AMINO-2,6-DIC...

~%

7-chloro-5-morpholin-4-yl-1H-pyrido[4,3-d]pyrimidin-4-one Structure

7-chloro-5-morp...

tert-Butyl (2,6-dichloropyridin-4-yl)carbamate Structure

tert-Butyl (2,6...

~%

7-chloro-5-morpholin-4-yl-1H-pyrido[4,3-d]pyrimidin-4-one Structure

7-chloro-5-morp...

2,6-Dichloro-4-({[(2-methyl-2-propanyl)oxy]carbonyl}amino)nicotinic acid Structure

2,6-Dichloro-4-...

~%

7-chloro-5-morpholin-4-yl-1H-pyrido[4,3-d]pyrimidin-4-one Structure

7-chloro-5-morp...

2,6-dichloropyridin-4-amine Structure

2,6-dichloropyr...

~%

7-chloro-5-morpholin-4-yl-1H-pyrido[4,3-d]pyrimidin-4-one Structure

7-chloro-5-morp...

2,6-Dichloro-4-({[(2-methyl-2-propanyl)oxy]carbonyl}amino)nicotinic acid Structure

2,6-Dichloro-4-...

~%

4-AMINO-2,6-DICHLORONICOTINIC ACID Structure

4-AMINO-2,6-DIC...

tert-Butyl (2,6-dichloropyridin-4-yl)carbamate Structure

tert-Butyl (2,6...

~%

4-AMINO-2,6-DICHLORONICOTINIC ACID Structure

4-AMINO-2,6-DIC...

2,6-dichloropyridin-4-amine Structure

2,6-dichloropyr...

~%

4-AMINO-2,6-DICHLORONICOTINIC ACID Structure

4-AMINO-2,6-DIC...

4-AMINO-2,6-DICHLORONICOTINAMIDE Structure

4-AMINO-2,6-DIC...

Triethyl orthoformate Structure

Triethyl orthof...

~%

5,7-Dichloropyrido[4,3-d]pyrimidin-4(1H)-one Structure

5,7-Dichloropyr...

tert-Butyl (2,6-dichloropyridin-4-yl)carbamate Structure

tert-Butyl (2,6...

~%

5,7-Dichloropyrido[4,3-d]pyrimidin-4(1H)-one Structure

5,7-Dichloropyr...

2,6-Dichloro-4-({[(2-methyl-2-propanyl)oxy]carbonyl}amino)nicotinic acid Structure

2,6-Dichloro-4-...

~%

5,7-Dichloropyrido[4,3-d]pyrimidin-4(1H)-one Structure

5,7-Dichloropyr...

4-AMINO-2,6-DICHLORONICOTINIC ACID Structure

4-AMINO-2,6-DIC...

~%

5,7-Dichloropyrido[4,3-d]pyrimidin-4(1H)-one Structure

5,7-Dichloropyr...

2,6-dichloropyridin-4-amine Structure

2,6-dichloropyr...

~%

5,7-Dichloropyrido[4,3-d]pyrimidin-4(1H)-one Structure

5,7-Dichloropyr...

4-AMINO-2,6-DICHLORONICOTINIC ACID Structure

4-AMINO-2,6-DIC...

~%

5,7-dichloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidine Structure

5,7-dichloro-4-...

tert-Butyl (2,6-dichloropyridin-4-yl)carbamate Structure

tert-Butyl (2,6...

~%

5,7-dichloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidine Structure

5,7-dichloro-4-...

2,6-Dichloro-4-({[(2-methyl-2-propanyl)oxy]carbonyl}amino)nicotinic acid Structure

2,6-Dichloro-4-...

~%

5,7-dichloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidine Structure

5,7-dichloro-4-...

2,6-dichloropyridin-4-amine Structure

2,6-dichloropyr...

~%

5,7-dichloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidine Structure

5,7-dichloro-4-...

4-AMINO-2,6-DICHLORONICOTINAMIDE Structure

4-AMINO-2,6-DIC...

Triethyl orthoacetate Structure

Triethyl orthoa...

~39%

5,7-dichloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidine Structure

5,7-dichloro-4-...

morpholine Structure

5,7-dichloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidine Structure

5,7-dichloro-4-...

~%

4-(7-chloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidin-5-yl)morpholine Structure

4-(7-chloro-4-e...

4-AMINO-2,6-DICHLORONICOTINIC ACID Structure

4-AMINO-2,6-DIC...

~%

4-(7-chloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidin-5-yl)morpholine Structure

4-(7-chloro-4-e...

4-AMINO-2,6-DICHLORONICOTINAMIDE Structure

4-AMINO-2,6-DIC...

~%

4-(7-chloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidin-5-yl)morpholine Structure

4-(7-chloro-4-e...

tert-Butyl (2,6-dichloropyridin-4-yl)carbamate Structure

tert-Butyl (2,6...

~%

4-(7-chloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidin-5-yl)morpholine Structure

4-(7-chloro-4-e...

2,6-Dichloro-4-({[(2-methyl-2-propanyl)oxy]carbonyl}amino)nicotinic acid Structure

2,6-Dichloro-4-...

~%

4-(7-chloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidin-5-yl)morpholine Structure

4-(7-chloro-4-e...

2,6-dichloropyridin-4-amine Structure

2,6-dichloropyr...

~%

4-(7-chloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidin-5-yl)morpholine Structure

4-(7-chloro-4-e...

4-AMINO-2,6-DICHLORONICOTINIC ACID Structure

4-AMINO-2,6-DIC...

~%

7-chloro-4-ethoxy-2-methyl-5-phenylpyrido[4,3-d]pyrimidine Structure

7-chloro-4-etho...

4-AMINO-2,6-DICHLORONICOTINAMIDE Structure

4-AMINO-2,6-DIC...

~%

7-chloro-4-ethoxy-2-methyl-5-phenylpyrido[4,3-d]pyrimidine Structure

7-chloro-4-etho...

tert-Butyl (2,6-dichloropyridin-4-yl)carbamate Structure

tert-Butyl (2,6...

~%

7-chloro-4-ethoxy-2-methyl-5-phenylpyrido[4,3-d]pyrimidine Structure

7-chloro-4-etho...

2,6-Dichloro-4-({[(2-methyl-2-propanyl)oxy]carbonyl}amino)nicotinic acid Structure

2,6-Dichloro-4-...

~%

7-chloro-4-ethoxy-2-methyl-5-phenylpyrido[4,3-d]pyrimidine Structure

7-chloro-4-etho...

2,6-dichloropyridin-4-amine Structure

2,6-dichloropyr...

~%

7-chloro-4-ethoxy-2-methyl-5-phenylpyrido[4,3-d]pyrimidine Structure

7-chloro-4-etho...

5,7-dichloro-4-ethoxy-2-methylpyrido[4,3-d]pyrimidine Structure

5,7-dichloro-4-...

Tri-n-butylphenyltin Structure

Tri-n-butylphenyltin

~%

7-chloro-4-ethoxy-2-methyl-5-phenylpyrido[4,3-d]pyrimidine Structure

7-chloro-4-etho...