4-Methylmorpholine → N-(2-Amino-2-ethylbutyl)-8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxamide

HRID 2275903Notes

Reaction equation

HRID 2275903 reaction equation
[CH2:1]([C:3]([NH2:8])([CH2:6][CH3:7])[CH2:4][NH2:5])[CH3:2].[F:9][C:10]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:11]=1[CH2:12][O:13][C:14]1[C:15]2[N:16]([C:21]([C:25](O)=[O:26])=[C:22]([CH3:24])[N:23]=2)[CH:17]=[C:18]([CH3:20])[CH:19]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1>CN(C=O)C.O.C(O)(C(F)(F)F)=O>[NH2:8][C:3]([CH2:6][CH3:7])([CH2:1][CH3:2])[CH2:4][NH:5][C:25]([C:21]1[N:16]2[CH:17]=[C:18]([CH3:20])[CH:19]=[C:14]([O:13][CH2:12][C:11]3[C:28]([F:32])=[CH:29][CH:30]=[CH:31][C:10]=3[F:9])[C:15]2=[N:23][C:22]=1[CH3:24])=[O:26]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 432996Diethylethylene diamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 867178848-[(2,6-Difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 86717988N-(2-Amino-2-ethylbutyl)-8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22392675Trifluoroacetic acid waterSolvent

Procedure

70 mg (0.60 mmol) of 2-ethylbutane-1,2-diamine were added to 100 mg (0.30 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid Example 21A, 145 mg (0.45 mmol) of TBTU and 0.13 ml (1.20 mmol) of 4-methylmorpholine in DMF (1.9 ml), and the reaction mixture was stirred at RT overnight. The mixture was then diluted with water/TFA and purified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA). After concentration, the residue was taken up in dichloromethane and washed twice with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted twice with dichloromethane. The combined organic phases were dried over sodium sulphate, filtered off, concentrated and lyophilized. This gave 110 mg (85% of theory, purity 100%) of the target compound.

Workup

  1. custompurified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA)
  2. concentrationAfter concentration
  3. washwashed twice with saturated aqueous sodium bicarbonate solution
  4. extractionThe aqueous phase was extracted twice with dichloromethane
  5. dry with materialThe combined organic phases were dried over sodium sulphate
  6. filtrationfiltered off
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1fdaa6dca7ee488cb48491d82e27f4f3
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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