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. 2020 Jul 22;25(15):3321. doi: 10.3390/molecules25153321

Scheme 4.

Scheme 4

Synthetic strategies to synthesize tofacitinib. Reagents and conditions: (A) (a) acetyl chloride, acetone; (b) benzyl chloride, toluene; (c) NaBH4, MeOH, H2O; (d) HCl; (e) titanium(IV) tetraisopropoxide, NH2Me, NaBH4, MeOH; (f) L-DTTA, MeOH−H2O (1:1); (g) (i) 6-chloro-7-deazapurine tosilate, K2CO3, H2O and (ii) KOH, MeOH or NaOH sutured solution; (h) Pd/C, H2O, AcOH or Pd(OH)2/C, TFA, MeOH and (i) ethylcyano acetate, DBU. (B) (a) (MeO)2CO, NaH, THF; (b) Rh/C, H2, AcOH, (c) PhCH2Br, K2CO3, HCl/EtOH and (d) Red-Al, toluene. (C) (a) BnCl; (b) NaBH4, EtOH:H2O; (c) TFA, m-CPBA, DCM; (d) NaN3, AcOH; (e) (i) Ph3P, toluene, (ii) Boc2O and (f) LiAlH4, THF. (D) (a) LiAlH4, THF and (b) 6-methylamino-7-deazapurine, DIAD, Ph3P, 1,4-dioxane.