Phosphorus oxychloride → 6-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido(4,3-d)pyrimidine

Participants

Reaction Steps

Various 4-alkylamino-6-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidines are prepared using a general procedure shown in Scheme 3. 6-Benzyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4(3H)-one is treated with POCl3 to give 6-benzyl-4-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine which is treated with sodium methoxide to give 6-benzyl-4-methoxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. Debenzylation and reacting the product with an appropriate 2-halo-pyridine under SNAr or Buchwald coupling reaction conditions gives the 4-methoxy-6-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine which is reacted with POCl3/POBr3. Displacement of the resultant 4-halo group using various alkylamines via SNAr displacement can afford various 4-alkylamino-6-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidines.

Provenance & Evidence