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

HRID 2275883Notes

Reaction equation

HRID 2275883 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:15][CH2:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])[C:5]2[N:6]([C:8]([C:12](O)=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.F[B-](F)(F)F.N1(O[C+](N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1.[CH3:54][C:55]([NH2:59])([CH3:58])[CH2:56][NH2:57]>CN(C=O)C>[NH2:59][C:55]([CH3:58])([CH3:54])[CH2:56][NH:57][C:12]([C:8]1[N:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[C:4]([O:15][CH2:16][C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[F:24])[C:5]2=[N:10][C:9]=1[CH3:11])=[O:13]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 131282-MethylpropylenediamineHCID 867178796-Chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acidHCID 178484679HCID 178484679, compound

Product 1

HCID 86717962N-(2-Amino-2-methylpropyl)-6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]-pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

70 mg of 6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid (0.20 mmol), 96 mg (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU, 0.30 mmol) and 80 mg of 4-methylmorpholine (0.79 mmol) were initially charged in 1 ml of DMF. 35 mg of 2-methylpropane-1,2-diamine (0.40 mmol) were then added, and the mixture was stirred at RT overnight. The reaction solution was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The product was taken up in ethyl acetate and washed twice with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted twice with ethyl acetate, the combined organic phases were dried over sodium sulphate and filtered. The filtrate was concentrated and lyophilized. This gave 38 mg of the title compound (45% of theory).

Workup

  1. customThe reaction solution was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
  2. washwashed twice with saturated aqueous sodium bicarbonate solution
  3. extractionThe aqueous phase was extracted twice with ethyl acetate
  4. dry with materialthe combined organic phases were dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-1d188edc41ed4a308b34803368412fb9
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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