ChemicalBook CAS DataBase List 2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one

2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one synthesis

4synthesis methods

Product Name:2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one
CAS Number:1013916-37-4
Molecular formula:C13H14ClN3O
Molecular Weight:263.72

5-broMo-2-chloro-N-cyclopentylpyriMidin-4-aMine

733039-20-8

107-93-7

2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one

1013916-37-4

To the reaction vessel was added 5-bromo-2-chloro-N-cyclopentyl-4-pyrimidinamine (10.0 g, 1.0 eq.) and N-methylpyrrolidone (NMP, 50 mL, 5.0 vol.) at room temperature. Subsequently, crotonic acid (4.7 g, 1.5 eq.) and triethylamine (20.2 mL, 4.0 eq.) were added to the reaction mixture. The vessel was degassed and purged three times with nitrogen. Palladium acetate (Pd(OAc)2, 0.25 g, 0.03 eq.) was added to the degassed reaction mixture. The vessel was again degassed and purged with nitrogen three times in the same manner. The reaction mixture was heated to 65 °C and stirred continuously until the feedstock was completely consumed (at least 6 hours). Then, acetic anhydride (6.8 mL, 2.0 eq.) was added to the reaction mixture. The reaction was kept at 65 °C until the feedstock was completely consumed (usually takes 1-2 hours). Upon completion of the reaction, the mixture was cooled to 20 °C and water (100 mL, 10 v/v) was added to dissolve the triethylamine-HBr salt while 2-chloro-8-cyclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7(8H)-one was precipitated. The precipitate was stirred at 20°C for 1 hour. The solid was collected by filtration and washed sequentially with a mixture of water (20 mL, 2.0 v/v) and isopropanol/water (4:1, 50 mL, 5.0 v/v). Finally, the crude product was vacuum dried at 55-70 °C to afford 2-chloro-8-cyclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7(8H)-one (7.8 g, 81% yield) as a tan to gray solid.

733039-20-8 Synthesis

733039-20-8
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$6.00/1g

107-93-7
326 suppliers
$11.19/100G

1013916-37-4
266 suppliers
$25.00/5g

Yield:1013916-37-4 81%

Reaction Conditions:

Stage #1:5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine;(E)-but-2-enoic acid with palladium diacetate;triethylamine in 1-methyl-pyrrolidin-2-one at 65;Inert atmosphere;
Stage #2: with acetic anhydride in 1-methyl-pyrrolidin-2-one at 65;Inert atmosphere;

Steps:

2.B Preparation of 2-chloro-8-cvclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one
To a vessel was added 5-bromo-2-chloro-6-cyclopentylamino-pyridimidine (10.0 g, 1.0 equiv.) along with N-methylpyrrolidone (NMP) (50 mL, 5.0 vol.) at ambient temperature. To the reaction mixture was added crotonic acid (4.7 g, 1.5 equiv.) and triethylamine (20.2 mL, 4.0 equiv.). The vessel was degassed and purged three times with nitrogen. To the degassed reaction mixture was added Pd(OAc)₂(0.25 g, 0.03 equiv.). The vessel was degassed and purged three times with nitrogen using the same method as step 3. The mixture was heated to 65°C and allowed to stir until starting material was consumed (at least 6 hours).Acetic anhydride (6.8 mL, 2.0 equiv) was added to the reaction mixture. The reaction was allowed to react at 65 °C until starting material was consumed (usually 1-2 hours). The reaction mixture was cooled to 20°C and H₂0 (100 mL, 10 vol) was added to dissolve triethylamine-HBr salts and precipitate out 2-chloro-8-cyclopentyl-5-methyl-8/-/- pyrido[2,3-c]pyrimidin-7-one. The material was granulated at 20 °C for 1 hour. The solids were filtered and washed with H₂0 (20 mL, 2.0 vol), and a 4: 1 mixture of isopropanol/H₂0 (50 mL, 5.0 vol). The crude product was dried under vacuum at 55-70°C to give 2-chloro-8-cyclopentyl-5- methyl-8/-/-pyrido[2,3-c]pyrimidin-7-one, (7.8 g; 81 %) as a tan to gray solid.

References:

PFIZER INC.;CHEKAL, Brian Patrick;IDE, Nathan D. WO2014/128588, 2014, A1 Location in patent:Page/Page column 34; 35

FullText

3724-65-0 Synthesis