Phosphorus oxychloride → 6-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido(4,3-d)pyrimidine
Reaction equation
[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][NH:14][C:15](=O)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:21]>>[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][N:14]=[C:15]([Cl:21])[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
Procedure
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.
Sources & evidence
- ORD record
- ord-6ff3aeccde9a43949e0b4bfb96f38a4e
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08653091B2
Reaction notes
Loading…