Efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines by a double annulation strategy from alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals.
A convenient and efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines via a double [5 + 1] annulation strategy starting from easily available alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals 1 and cheap reagents (NH4OAc, DMF, and POCl3) has been developed. In the first step of the double annulation route, 2-amino-3-carbamoyl-5,6-dihydro-4-pyridones 2 were created in high to excellent yields by a formal [5C + 1N] annulation reaction of ketene-(S,S)-acetals 1 with ammonia (from ammonium acetate). In the second step of the double annulation strategy, the highly functionalized dihydropyrido[2,3-d]pyrimidine derivatives, 7,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-ones 3 (when R1 = aryl) and 7,8-dihydropyrido[2,3-d]pyrimidines 4 (when R1 = H), were constructed, respectively, in fair to good yields by reacting 2 with excessive Vilsmeier reagent (DMF/POCl3). A mechanism involved in the second [5 + 1] annulation step, including a formal [5 + 1] annulation and accompanied chlorovinylation, chloroformylation, amination, and aromatization reactions, is proposed.
Zhao
Lei
L
Department of Chemistry, Northeast Normal University, Changchun 130024, China.
Liang
Fushun
F
Bi
Xihe
X
Sun
Shaoguang
S
Liu
Qun
Q
D000080:Acetals / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D005030:Ethylenes / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry*
D000080:Acetals; D000475:Alkenes; D005030:Ethylenes; D007659:Ketones; D011743:Pyrimidines; D006859:Hydrogen; C030986:pyrimidine; C008223:ketene