Cesium carbonate → HCID 76281424, compound

HRID 1501373Notes

Reaction equation

HRID 1501373 reaction equation
[NH2:1][C:2]1([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[N:13]=[C:14]4[CH:19]=[CH:18][C:17]([OH:20])=[N:16][N:15]4[C:21]=3[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:34][O:35][C:36](=[O:39])[CH2:37]Br>CN(C=O)C.O>[NH2:1][C:2]1([C:6]2[CH:7]=[CH:8][C:9]([C:12]3[N:13]=[C:14]4[CH:19]=[CH:18][C:17]([O:20][CH2:37][C:36]([O:35][CH3:34])=[O:39])=[N:16][N:15]4[C:21]=3[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:10][CH:11]=2)[CH2:5][CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 178507127HCID 178507127, compound

Product 1

HCID 76281424HCID 76281424, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[4-(1-aminocyclobutyl)phenyl]-3-phenylimidazo[1,2-b]pyridazin-6-ol that was prepared in a manner analgous to that described for Example 79 (0.093 g, 0.26 mmol) in DMF (2.5 mL) was added cesium carbonate (0.26 g, 0.79 mmol, 3.0 equiv) and bromoacetic acid methyl ester (0.03 mL, 0.31 mmol, 1.20 equiv). The resulting mixture was stirred at room temperature for 1 h, then was warmed to 60° C. for 3 h. The resulting mixture was diluted with water (10 mL). The aqueous mixture was extracted with EtOAC (3×10 mL). The combined organic phases were dried (Na2SO4 anh.) and concentrated under reduced pressure. The resulting material was further purified using preparative HPLC (Agilent Prep 1200 equipped with 2× Prep Pump, DLA, MWD, ELSD and Prep FC using an XBrigde C18 5 μm 100×30 mm column; gradient from 100% water with 0.1% HCO2H to 70% water with 0.1% HCO2H/30% MeOH over 1.0 min, gradient to 30% water with 0.1% HCO2H/70% MeOH over 7.0 min, gradient to 100% MeOH over 0.1 min, 100% MeOH 1.9 min) to give methyl ({2-[4-(1-aminocyclobutyl)phenyl]-3-phenylimidazo[1,2-b]pyridazin-6-yl}oxy)acetate (0.056 g, 49%):

Workup

  1. temperaturewas warmed to 60° C. for 3 h
  2. extractionThe aqueous mixture was extracted with EtOAC (3×10 mL)
  3. dry with materialThe combined organic phases were dried (Na2SO4 anh.)
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting material was further purified
  6. customequipped with 2× Prep Pump, DLA, MWD, ELSD and Prep FC
  7. waitgradient from 100% water with 0.1% HCO2H to 70% water with 0.1% HCO2H/30% MeOH over 1.0 min
  8. waitgradient to 30% water with 0.1% HCO2H/70% MeOH over 7.0 min
  9. waitgradient to 100% MeOH over 0.1 min

Sources & evidence

ORD record
ord-d3ef994511c348dda380de65467436b1
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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