Efficient synthesis of 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones

A process for preparing a compound of formula IIIb:

• comprising:
• (c) contacting the compound of formula IIIa with 2-hydroxy-pyridine in the presence of a catalyst, a bidentate-diamine ligand, and a third aprotic solvent to form a compound of formula IIb;
• wherein:
• ring D is selected from phenyl, 2-fluorophenyl, 3-chlorophenyl, and 4-methoxyphenyl;
• B is selected from F, Cl, Br, I, OSO2CF3, and OSO2Ph-p-Me;
• R1a is selected from CH3, CH2CH3, CH2CH2CH3, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, OCH2CH2CH2CH3, OCH(CH3)CH2CH3, OCH2CH(CH3)2, and OC(CH3)3;
• R1b is C1-6 alkyl;
• ring A is substituted with 0-1 R4;
• and
• R4 is selected from H, OH, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, F, Cl, Br, I, CH CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH2CH(CH3)2, CH(CH3)CH2CH3, CH(CH3)3, —CN, and CF3.

A process for preparing a compound of formula IIIc:

• comprising:
• (d) contacting the compound of formula IIa with 2-hydroxy-pyridine in the presence of a catalyst and a fourth aprotic solvent to form a compound of formula IIb;
• (e) contacting a compound of formula I with a compound of formula IIb in the presence of a second base to form a compound of formula IIIc;
• wherein:
• Z is selected from Cl, Br, I, OSO2CF3, OSO2Me, OSO2Ph, and OSO2Ph-p-Me;
• ring D is selected from phenyl, 2-fluorophenyl, 3-chlorophenyl, and 4-methoxyphenyl;
• R1a is selected from NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, CH3, CH2CH3, CH2CH2CH3, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, OCH2CH2CH2CH3, OCH(CH3)CH2CH3, OCH2CH(CH3)2, and OC(CH3)3;
• R is selected from Cl, Br, I, C1-6 alkoxy, and NR1R2;
• R1 and R2 are independently selected from C1-6 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, and benzyl;
• alternatively, NR1R2 is a 3-8 membered ring consisting of:
• carbon atoms, N, and 0-1 O atoms;
• ring A is substituted with 0-1 R4;
• B is selected from F, Cl, Br, I, OSO2CF3, and OSO2Ph-p-Me;
• and
• R4 is selected from H, OH, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, F, Cl, Br, I, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH2CH(CH3)2, CH(CH3)CH2CH3, CH(CH3)3, —CN, and CF3.

A process for preparing a compound of formula IV:

• comprising:
• (f) contacting the compound of formula IIIc with a formamide in the presence of a third base to form a compound of formula IV;
• wherein:
• the formamide is HC(O)NHR5;
• the third base is an alkoxide;
• ring D is selected from phenyl, 2-fluorophenyl, 3-chlorophenyl, and 4-methoxyphenyl;
• R1a is selected from OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, OCH2CH2CH2CH3, OCH(CH3)CH2CH3, OCH2CH(CH3)2, and OC(CH3)3;
• ring A is substituted with 0-1 R4;
• B is 2-oxo-pyridyl;
• R4 is selected from H, OH, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, F, Cl, Br, I, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH2CH(CH3)2, CH(CH3)CH2CH3, CH(CH3)3, —CN, and CF3;
• and
• R5 is selected from H, CH3, and CH2CH3.

A process for preparing a compound of formula IIIb:

• comprising:
• (g) contacting a compound of formula III with an R1b-metal reagent to form a compound of formula IIIc;
• wherein:
• ring D is selected from phenyl, 2-fluorophenyl, 3-chlorophenyl, and 4-methoxyphenyl;
• R1a is selected from CH3, CH2CH3, CH2CH2CH3, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, OCH2CH2CH2CH3, OCH(CH3)CH2CH3, OCH2CH(CH3)2, and OC(CH3)3;
• R1b is C1-6 alkyl;
• ring A is substituted with 0-1 R4;
• R4 is selected from H, OH, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, F, Cl, Br, I, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH2CH(CH3)2, CH(CH3)CH2CH3, CH(CH3)3, —CN, and CF3.