托法替布枸橼酸盐有关物质的合成

Synthesis of the Related Substances of Tofacitinib Citrate

为控制托法替布枸橼酸盐的质量,分别合成了6个工艺杂质——4-(4-氯吡咯并[2,3-d]嘧啶-7-基)-7H-吡咯并[2,3-d]嘧啶、N-甲基-N-[(3R,4R)-4-甲基-1-苄基-3-哌啶基]-7-甲基-吡咯并[2,3-d]嘧啶-4-胺、3-[(3R,4R)-4-甲基-3-[N-甲基-(7H-吡咯并[2,3-d]-4,5-二氢嘧啶-4-基)氨基]哌啶-1-基]-3-氧代丙腈、3-[(3R,4R)-4-甲基-3-[N-甲基-(7-甲基-吡咯并[2,3-d]嘧啶-4-基)氨基]哌啶-1-基]-3-氧代丙腈、N-甲基-N-[(3R,4R)-1,4-二甲基-3-哌啶基]-7H-吡咯并[2,3-d]嘧啶-4-胺及N-甲基-N-[(3R,4R)-1,4-二甲基-3-哌啶基]-7-甲基-吡咯并[2,3-d]嘧啶-4-胺,其结构均经~1H NMR和MS确证,可作为质量研究的对照物。

To perform the quality control of tofacitinib citrate, six related substances were prepared and confirmed by 1H NMR and MS. These substances were 4-（4-chloro-pyrrolo [2,3-d]pyrimidin-7-yl）-7H-pyrrolo [2,3- d] pyrimidine, N-methyl-N- E （3R,4R） - 1 -benzyl-4-methylpiperidin- 3-yl] -7-methyl-pyrrolo E2,3-d] pyrimidin-4- amine, 3- [ （3R,4R） -4-methyl-3- IN-methyl- （7H-pyrrolo [2,3-d] -4,5-dihydropyrimidin-4-yl） amino] piperidin- 1 -yl] -3- oxopropanenitrile, 3- [ （3R,4R） -4-methyl-3- IN-methyl- （7-methyl-pyrrolo [2,3-dl pyrimidin-4-yl） amino] piperidin- 1 - yl]-3-oxopropanenitrile, N-methyl-N- U （3R,4R） -1,4-dimethylpiperidin-3-yl]-7H-pyrrolo U2,3-d] pyrimidin-4-amine and N-methyl-N- [（3R,4R） - 1,4-dimethylpiperidin-3-yl] -7-methyl-pyrrolo E2,3-d] pyrimidin-4-amine.