Water → Tert-butyl (6-(3-fluoro-4-(2-oxopyrrolidin-1-yl)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate

HRID 40219Notes

Reaction equation

HRID 40219 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[N:9][N:10]=2)[N:7]=1.[F:20][C:21]1[CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=[CH:23][C:22]=1[N:36]1[CH2:40][CH2:39][CH2:38][C:37]1=[O:41].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1.O>>[F:20][C:21]1[CH:26]=[C:25]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[N:9][N:10]=3)[N:7]=2)[CH:24]=[CH:23][C:22]=1[N:36]1[CH2:40][CH2:39][CH2:38][C:37]1=[O:41]

Participants

6

Reactant 5

HCID 962WaterHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 57691353(3-Fluoro-4-(2-oxopyrrolidin-1-YL)phenyl)boronic acid pinacol esterHCID 57691389tert-Butyl ((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)carbamate

Product 1

HCID 57691433Tert-butyl (6-(3-fluoro-4-(2-oxopyrrolidin-1-yl)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamateYield 51.9%

Procedure

A 48 mL sealed tube was charged with tert-butyl (6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (0.150 g, 0.529 mmol), 1-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrrolidin-2-one (0.242 g, 0.793 mmol), PdCl2(dppf)-CH2Cl2Adduct (0.0432 g, 0.0529 mmol), cesium carbonate (0.689 g, 2.11 mmol), 1,4-dioxane (3.62 ml, 42.3 mmol), and water (0.905 ml, 50.2 mmol), flushed with argon, sealed, then placed in a 80° C. oil bath for 5 hours. The contents were transferred to a flask and concentrated. The solid was triturated with water to give a red residue, which was purified by MPLC using a 40 g RediSep column, eluting with 2-6% MeOH/DCM over 40 minutes. tert-butyl (6-(3-fluoro-4-(2-oxopyrrolidin-1-yl)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (0.117 g, 51.9% yield) was isolated as a tan solid.

Workup

  1. customA 48 mL sealed tube
  2. customflushed with argon
  3. customsealed
  4. customplaced in a 80° C.
  5. customfor 5 hours
  6. customThe contents were transferred to a flask
  7. concentrationconcentrated
  8. customThe solid was triturated with water
  9. customto give a red residue, which
  10. customwas purified by MPLC
  11. washeluting with 2-6% MeOH/DCM over 40 minutes

Sources & evidence

ORD record
ord-4c471428a0a849dba4d8b42d3e1df5ea
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Reaction notes

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