Abstract: The invention relates to a novel process for the preparation of chiral pyrrolo triazole alcohols of the formula I wherein X is a halogen atom, n is an integer of 1, 2 or 3 and wherein the spiral bond “” stands for “” or for “” or mixtures of the enantiomers. The chiral pyrrolo triazole alcohols of the formula I are versatile intermediates for the preparation of compounds that have the potential to serve as active pharmaceutical ingredients in drugs.

Abstract: The invention relates to processes for the synthesis of 2-(3-cyano-5-fluorophenyl)-2-methylpropanoic acid and its use as intermediate in the preparation of GLP-1R/GIPR agonists. The invention also relates to a process of preparing a GLP-1R/GIPR agonist.

Abstract: Provided herein are methods of synthesizing quinazoline compounds comprising at least one atropisomeric center.

Abstract: Provided herein are methods to synthesize compounds useful in the treatment of cancer where such compounds comprise a quinazolinyl core moiety and at least one stereoisomeric or atropisomeric moiety.

Abstract: A manufacturing process to a bis-mesylate salt 1b of the pan-RAF inhibitor 4-amino-n-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl) thieno[3,2-d]pyrimidine-7-carboxamide. The process features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2and a highly chemoselective Pt/V/C-catalyzed nitro group reduction to access penultimate intermediate 7. The final amide coupling of 7 and 2 was accomplished by a mild and safe protocol employing N,N,N?,N?-tetramethylchloroformamidinium hexafluorophosphate (TCFH) as the coupling reagent, to produce a 1:1 adduct of the freebase and THF. The adduct afforded compound 1b with excellent yield, purity, and form stability on a multikilogram production scale after reaction with MsOH and recrystallization. The methods are able to produce a compound having upwards of 95% purity.

Abstract: Provided herein are methods of synthesizing quinazoline compounds comprising at least one atropisomeric center.

Abstract: The invention provides crystalline forms of 2?-(7,7-dimethyl-1?H,7H-spiro[furo[3,4-b]pyridine-5,4?-piperidin]-1?-yl)-1,3-dihydro-4?H-spiro[indene-2,5?-[1,3]oxazol]-4?-one, and a process for converting Form A to Form B for use in medicaments for treatment of anxiety, depression, irritability, impaired social interactions and psychomotor coordination, and other indications. The invention further provides processes to manufacture 2?-(7,7-dimethyl-1?H,7H-spiro[furo[3,4-b]pyridine-5,4?-piperidin]-1?-yl)-1,3-dihydro-4?H-spiro[indene-2,5?-[1,3]oxazol]-4?-one. Also disclosed are compounds useful as intermediates in the methods of the invention.

Abstract: Provided herein are methods to synthesize compounds useful in the treatment of cancer where such compounds comprise a quinazolinyl core moiety and at least one stereoisomeric or atropisomeric moiety.

Abstract: A manufacturing process to a bis-mesylate salt 1b of the pan-RAF inhibitor 4-amino-n-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide. The process features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2 and a highly chemoselective Pt/V/C-catalyzed nitro group reduction to access penultimate intermediate 7. The final amide coupling of 7 and 2 was accomplished by a mild and safe protocol employing N,N,N?,N?-tetramethylchloroformamidinium hexafluorophosphate (TCFH) as the coupling reagent, to produce a 1:1 adduct of the freebase and THF. The adduct afforded compound 1b with excellent yield, purity, and form stability on a multikilogram production scale after reaction with MsOH and recrystallization. The methods are able to produce a compound having upwards of 95% purity.

Abstract: Provided herein are methods to synthesize compounds useful in the treatment of cancer where such compounds comprise a quinazolinyl core moiety and at least one stereoisomeric or atropisomeric moiety.

Abstract: A manufacturing process to a bis-mesylate salt 1b of the pan-RAF inhibitor 4-amino-n-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide. The process features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2 and a highly chemoselective PtN/C-catalyzed nitro group reduction to access penultimate intermediate 7. The final amide coupling of 7 and 2 was accomplished by a mild and safe protocol employing N,N,N?,N?-tetramethylchloroformamidinium hexafluorophosphate (TCFH) as the coupling reagent, to produce a 1:1 adduct of the freebase and THF. The adduct afforded compound 1b with excellent yield, purity, and form stability on a multikilogram production scale after reaction with MsOH and recrystallization. The methods are able to produce a compound having upwards of 95% purity.

Abstract: Provided herein are methods of synthesizing quinazoline compounds comprising at least one atropisomeric center.