Process for preparing pyrido[2,3-d]pyrimidin-7-one and 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one derivatives

A compound of the formula:

• wherein
• G1 is NH;
• G2 is nitrogen;
• Rx is chloro, bromo, iodo, or O—S(O)2CF3;
• X is R2, OR2′, S(O)mR2′, (CH2)n′N(R11)S(O)mR2′, (CH2)n′N(R11)C(O)R2′, (CH2)n′NR4R14 or (CH2)n′N(R2′)(R2″), or N(R10′)—Rh—NH—C(═N—CN)NRqRq′;
• X1 is N(R11), O, S(O)m, or CR10R20;
• Rh is selected from an optionally substituted C1-10 alkyl, —CH2—C(O)—CH2—, —CH2CH2—O—CH2—CH2—, —CH2—C(O)N(R10′)CH2—CH2—, —CH2—N(R10′)C(O)CH2—, —CH2—CH(OR10′)—CH2, —CH2—C(O)O—CH2—CH2—, or —CH2—CH2—O—C(O)CH2—;
• Rq and Rq′ are independently selected at each occurrence from hydrogen, C1-10 alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-10alkyl, C5-7 cycloalkenyl, C5-7 cycloalkenyl-C 1-10alkyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic, or a heterocyclylC1-10 alkyl moiety, wherein all of the moieties, excluding hydrogen, are optionally substituted, or Rq and Rq′ together with the nitrogen to which they are attached form a 5 to 7 membered optionally substituted ring, which ring may contain an additional heteroatom selected from oxygen, nitrogen or sulfur;
• R2 is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic, or a heterocyclylC1-10 alkyl moiety, and wherein each of these moieties, excluding hydrogen, may be optionally substituted;
• or R2 is the moiety (CR10R20)q′X1(CR10R20)qC(A1)(A2)(A3), or C(A1)(A2)(A3);
• R2′ is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic, or a heterocyclylC1-10 alkyl moiety, and wherein each of these moieties, excluding hydrogen, may be optionally substituted;
• R2″ is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic, or a heterocyclylC1-10 alkyl moiety, and wherein these moieties, excluding hydrogen, may be optionally substituted;
• or
• wherein R2″ is the moiety (CR10R20)tX1(CR10R20)qC(A1)(A2)(A3);
• A1 is an optionally substituted C1-10 alkyl, heterocyclic, heterocyclic C1-10 alkyl, heteroaryl, heteroaryl C1-10 alkyl, aryl, or aryl C1-10 alkyl;
• A2 is an optionally substituted C1-10 alkyl, heterocyclic, heterocyclic C1-10 alkyl, heteroaryl, heteroaryl C1-10 alkyl, aryl, or aryl C1-10 alkyl;
• A3 is hydrogen or is an optionally substituted C1-10 alkyl;
• R3 is a C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl C1-10 alkyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic or a heterocyclylC1-10 alkyl moiety, and wherein each of these moieties may be optionally substituted;
• R4 and R14 are each independently selected from hydrogen, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylC1-4alkyl, aryl, aryl-C1-4 alkyl, heterocyclic, heterocyclic C1-4 alkyl, heteroaryl or a heteroaryl C1-4 alkyl moiety, and wherein each of these moieties, excluding hydrogen, may be optionally substituted;
• or the R4 and R14 together with the nitrogen which they are attached form an optionally substituted heterocyclic ring of 4 to 7 members, which ring optionally contains an additional heteroatom selected from oxygen, sulfur or nitrogen;
• R10 and R20 are independently selected from hydrogen or C1-4alkyl;
• R10′ is independently selected at each occurrence from hydrogen or C1-4alkyl;
• R11 is independently selected from hydrogen or C1-4alkyl;
• n′ is independently selected at each occurrence from 0 or an integer having a value of 1 to 10;
• m is independently selected at each occurrence from 0 or an integer having a value of 1 or 2;
• q is 0 or an integer having a value of 1 to 10;
• q′ is 0, or an integer having a value of 1 to 6;
• or
• t is an integer having a value of 2 to 6.