The author of 《Process Development and Scale Up of a Selective JAK3 Covalent Inhibitor PF-06651600》 were Tao, Yong; McWilliams, J. Christopher; Wiglesworth, Kristin E.; Girard, Kevin P.; Makowski, Teresa M.; Sach, Neal W.; Mustakis, Jason G.; Mehta, Ruchi; Trujillo, John I.; Chen, Xiaofeng; Li, Tangqing; Shi, Feng; Xie, Chengfu; Zhang, Qing. And the article was published in Organic Process Research & Development in 2019. Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The author mentioned the following in the article:
A scalable process for PF-06651600 was developed through successful enabling of the first generation synthesis. 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 diasteromeric 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-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one p-Toluenesulfonate, which is suitable for long-term storage and tablet formulation. All chromatog. purifications, including two chiral SFC chromatog. 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 were delivered to support clin. studies. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine)
2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia