Benzyl Bromide → HCID 86716505, compound

HRID 1501330Notes

Reaction equation

HRID 1501330 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:35])[C:5]2[N:6]([C:8]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:42](Br)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CN(C=O)C>[CH2:42]([O:35][C:4]1[C:5]2[N:6]([C:8]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:10]=2)[N:7]=[C:2]([Cl:1])[CH:3]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 178452599HCID 178452599, compound

Product 1

HCID 86716505HCID 86716505, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl {1-[4-(6-chloro-8-hydroxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate that was in a manner analgous to that described for Intermediate Example Int-16 (1.90 g, 3.87 mmol) in DMF (50 mL) was added cesium carbonate (6.88 g, 11.6 mmol, 3.0 equiv.) and benzyl bromide (0.58 mL, 4.84 mmol, 1.25 equiv.), and the resulting mixture was irradiated in a microwave apparatus at 140° C. for 90 min. The resulting mixture stirred at room temperature for 16 h. The resulting mixture was added to ice water 100 mL). The aqueous mixture was extracted with a 4:1 DCM/isopropanol solution (3×50 mL). The combined organic phases were dried (Na2SO4 anh.), and concentrated under reduced pressure. The resulting oil was triturated with ethanol to give tert-butyl (1-{4-[8-(benzyloxy)-6-chloro-3-phenylimidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutyl)carbamate as a powder (0.93 g, 41%):

Workup

  1. customthe resulting mixture was irradiated in a microwave apparatus at 140° C. for 90 min
  2. extractionThe aqueous mixture was extracted with a 4:1 DCM/isopropanol solution (3×50 mL)
  3. dry with materialThe combined organic phases were dried (Na2SO4 anh.)
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting oil was triturated with ethanol

Sources & evidence

ORD record
ord-94bd93a4be294b2fa363987b66658f96
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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