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

HRID 2275898Notes

Reaction equation

HRID 2275898 reaction equation
[CH3:1][C:2]([NH2:9])([CH2:5][CH:6]([CH3:8])[CH3:7])[CH2:3][NH2:4].[Cl:10][C:11]1[CH:12]=[C:13]([O:24][CH2:25][C:26]2[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=2[F:33])[C:14]2[N:15]([C:17]([C:21](O)=[O:22])=[C:18]([CH3:20])[N:19]=2)[CH:16]=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>[NH2:9][C:2]([CH3:1])([CH2:5][CH:6]([CH3:8])[CH3:7])[CH2:3][NH:4][C:21]([C:17]1[N:15]2[CH:16]=[C:11]([Cl:10])[CH:12]=[C:13]([O:24][CH2:25][C:26]3[C:27]([F:33])=[CH:28][CH:29]=[CH:30][C:31]=3[F:32])[C:14]2=[N:19][C:18]=1[CH3:20])=[O:22]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 30629272,4-Dimethylpentane-1,2-diamineHCID 867178796-Chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 90114332rac-N-(2-Amino-2,4-dimethylpentyl)-6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22392675Trifluoroacetic acid waterSolvent

Procedure

61 mg (0.47 mmol) of rac-2,4-dimethylpentane-1,2-diamine were added to 150 mg (0.43 mmol) of 6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 16A, 143 mg (0.45 mmol) of TBTU and 0.19 ml (1.70 mmol) of 4-methylmorpholine in DMF (1.5 ml), and the reaction mixture was stirred at RT overnight. 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. Saturated aqueous sodium bicarbonate solution was added to the residue, and the mixture was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulphate, filtered off and concentrated. This gave 162 mg (79% of theory, purity 96%) of the target compound.

Workup

  1. custompurified by prep
  2. additionRP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA)
  3. concentrationThe product fraction was concentrated
  4. additionSaturated aqueous sodium bicarbonate solution was added to the residue
  5. extractionthe mixture was extracted three times with dichloromethane
  6. dry with materialThe combined organic phases were dried over sodium sulphate
  7. filtrationfiltered off
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-de6ee47805364d629b4024e2793ffe6e
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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