Iodoethane → HCID 70817815, compound

HRID 1501332Notes

Reaction equation

HRID 1501332 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:20]=[C:21]4[C:26]([OH:27])=[CH:25][C:24]([C:28]([O:30][CH3:31])=[O:29])=[N:23][N:22]4[C:32]=3[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:39](I)[CH3:40].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C:9]1([C:13]2[CH:14]=[CH:15][C:16]([C:19]3[N:20]=[C:21]4[C:26]([O:27][CH2:39][CH3:40])=[CH:25][C:24]([C:28]([O:30][CH3:31])=[O:29])=[N:23][N:22]4[C:32]=3[C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)=[CH:17][CH:18]=2)[CH2:10][CH2:11][CH2:12]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 10796Cesium carbonateHCID 178498530HCID 178498530, compound

Product 1

HCID 70817815HCID 70817815, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of methyl 2-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-8-hydroxy-3-phenylimidazo[1,2-b]pyridazine-6-carboxylate that was in a manner analgous to that described for Intermediate Example Int-18 (0.16 g, 0.32 mmol), ethyl iodide (0.50 mL, 0.63 mmol, 2.0 equiv.) and cesium carbonate (0.31 g, 0.94 mmol, 3.0 equiv.) in DMF (6 mL) was stirred for 1 h at room temperature, followed by 3 h at 50° C. The reaction mixture was then added to ice water (20 mL). The aqueous mixture was extracted with a 4:1 DCM/isopropanol solution (2×25 mL). The combined organic phases were dried (Na2SO4 anh.) and concentrated under reduced pressure. The resulting material was purified using MPLC (Biotage Isolera; Snap 10 g cartridge, 80% hexane/20% EtOAc 3.0 min, gradient to 55% hexane/45% EtOAc 2.0 min, 55%/45% EtOAc 3.0 min, gradient to 4% hexane/96% EtOAc 5.5 min, gradient to 100% EtOAc 0.5 min, 100% EtOAc 7.2 min) to give methyl 2-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-8-ethoxy-3-phenylimidazo[1,2-b]pyridazine-6-carboxylate (0.072 g, 42%):

Workup

  1. extractionThe aqueous mixture was extracted with a 4:1 DCM/isopropanol solution (2×25 mL)
  2. dry with materialThe combined organic phases were dried (Na2SO4 anh.)
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting material was purified
  5. customMPLC (Biotage Isolera; Snap 10 g cartridge, 80% hexane/20% EtOAc 3.0 min, gradient to 55% hexane/45% EtOAc 2.0 min, 55%/45% EtOAc 3.0 min, gradient to 4% hexane/96% EtOAc 5.5 min, gradient to 100% EtOAc 0.5 min, 100% EtOAc 7.2 min)

Sources & evidence

ORD record
ord-4a20d870a38f403c9eefc6905a3182d0
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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