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 N-substituted 2-(4-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitriles are prepared using a general procedure shown above (Scheme 2). 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-benzonitrile under SNAR or Buchwald coupling reaction conditions give the 2-(4-methoxy-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile which is reacted with POCl3 or POBr3. Displacement of the resultant 4-chloro or 4-bromo group using appropriately substituted amines via SNAR displacement affords various N-substituted 2-(4-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitriles.
Sources & evidence
- ORD record
- ord-116081e152b8459ca36d2bfae07a9d91
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08076345B2
Reaction notes
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