1207853-23-3

Upstream product

• 323578-37-6 tert-butyl N-(6-methylpyridin-3-yl)carbamate 
• 80287-53-2 5-Amino-2-methylpyridine 
• 501-53-1 benzyl chloroformate 
• 1150618-39-5 cis/trans-tert-butyl (6-methylpiperidin-3-yl)carbamate 
• 1222491-53-3 tert-butyl (6-methylpiperidin-3-yl)carbamate 
• 1207853-21-1 phenylmethyl (2S,5R)-5-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-methyl-1-piperidinecarboxylate 

Downstream Products

• 1792180-81-4 (-) 1-((2S,5R)-5-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one 

Relevant academic research and scientific papers

PYRROLO[2,3-D]PYRIMIDINE TOSYLATE SALT, CRYSTALLINE FORM THEREOF AND MANUFACTURING PROCESS AND INTERMEDIATES THERETO

The present invention discloses a novel p-toluenesulfonic acid salt and a crystalline polymorphic Form 1 of said salt of 1-((2S,5R)-5-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one, pharmaceutical composition containing the same, as well as preparations and uses thereof. The present invention also discloses a novel phosphoric acid salt of 1-((2S,5R)-5-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one, pharma-ceutical composition containing the same, as well as preparations and uses thereof.

PYRROLO [2,3-d] PYRIMIDINE TOSYLATE, CRYSTALLINE FORMS THEREOF, AND PREPARATION METHOD AND INTERMEDIATE THEREOF

PROBLEM TO BE SOLVED: To provide a drug molecule in a novel or purer polymorphic form. SOLUTION: In the present invention, disclosed is a novel p-toluenesulfonate of 1-((2S,5R)-5-((7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino)-2-methyl piperidin-1-yl) prop-2-en-1-one and a crystalline polymorphic form 1 thereof, a pharmaceutical composition comprising the same, and their preparation and use. In the present invention, also disclosed is a novel phosphate of 1-((2S,5R)-5-((7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino)-2-methyl piperidin-1-yl) prop-2-en-1-one, a pharmaceutical composition comprising the same, and their preparation and use. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2020,JPOandINPIT

Process Development and Scale up of a Selective JAK3 Covalent Inhibitor PF-06651600

A scalable process for PF-06651600 (1) has been developed through successful enabling of the first generation syntheis. The synthesis highlights include the following: (1) replacement of costly PtO2 with a less expensive 5% Rh/C catalyst for a pyridine hydrogenation, (2) identification of a diasteroemeric salt crystallization to isolate the enantiomerically pure cis-isomer directly from a racemic mixture of cis/trans isomers, (3) a high yielding amidation via Schotten-Baumann conditions, and (4) critical development of a reproducible crystallization procedure for a stable crystalline salt (1·TsOH), which is suitable for long-term storage and tablet formulation. All chromatographic purifications, including two chiral SFC chromatographic separations, were eliminated. Combined with other improvements in each step of the synthesis, the overall yield was increased from 5% to 14%. Several multikilogram batches of the API have been delivered to support clinical studies.

6 SUBSTITUTED 2-HETEROCYCLYLAMINO PYRAZINE COMPOUNDS AS CHK-1 INHIBITORS

The present invention is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, their synthesis, and their use as CHK-1 inhibitors.