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

HRID 2275894Notes

Reaction equation

HRID 2275894 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([OH:18])=O)=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1.[CH3:53][C:54]([NH2:61])([CH2:57][CH:58]([CH3:60])[CH3:59])[CH2:55][NH2:56]>CN(C=O)C.O.C(O)(C(F)(F)F)=O>[NH2:61][C:54]([CH3:53])([CH2:57][CH:58]([CH3:60])[CH3:59])[CH2:55][NH:56][C:16]([C:12]1[N:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][C:3]3[C:19]([F:23])=[CH:20][CH:21]=[CH:22][C:2]=3[F:1])[C:7]2=[N:14][C:13]=1[CH3:15])=[O:18]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 30629272,4-Dimethylpentane-1,2-diamine2×HCID 867178728-((2,6-Difluorobenzyl)oxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 90114279rac-N-(2-Amino-2,4-dimethylpentyl)-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22392675Trifluoroacetic acid waterSolvent

Procedure

150 mg (0.47 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 3A were initially charged in DMF (1.7 ml), and 159 mg (0.50 mmol) of TBTU and 0.16 ml (1.41 mmol) of 4-methylmorpholine were added. 68 mg (0.52 mmol) of rac-2,4-dimethylpentane-1,2-diamine were then added, and the reaction mixture was stirred at RT overnight. Another 6.1 mg (0.04 mmol) of rac-2,4-dimethylpentane-1,2-diamine were added, and the reaction mixture was stirred at RT for 20 min. The mixture was diluted with water/TFA and purified by prep. RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA). The product fraction was concentrated. The residue was taken up in dichloromethane and a few drops of methanol and washed twice with saturated aqueous sodium bicarbonate solution, and the aqueous phase was extracted three times with dichloromethane. The organic phase was dried over sodium sulphate, filtered off and concentrated. This gave 126 mg (61% of theory, purity 97%) of the target compound.

Workup

  1. stirringthe reaction mixture was stirred at RT for 20 min
  2. custompurified by prep
  3. additionRP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA)
  4. concentrationThe product fraction was concentrated
  5. washa few drops of methanol and washed twice with saturated aqueous sodium bicarbonate solution
  6. extractionthe aqueous phase was extracted three times with dichloromethane
  7. dry with materialThe organic phase was dried over sodium sulphate
  8. filtrationfiltered off
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-3fc7c8e8cc8043528936de7841d1060c
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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