4-Methylmorpholine → HCID 90114467, compound

HRID 2275900Notes

Reaction equation

HRID 2275900 reaction equation
Cl.[F:2][C:3]([F:10])([F:9])[C:4]([CH3:8])([NH2:7])[CH2:5][NH2:6].[F:11][C:12]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[C:13]=1[CH2:14][O:15][C:16]1[C:17]2[N:18]([C:23]([C:27](O)=[O:28])=[C:24]([CH3:26])[N:25]=2)[CH:19]=[C:20]([CH3:22])[CH:21]=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>[NH2:7][C:4]([CH3:8])([C:3]([F:10])([F:9])[F:2])[CH2:5][NH:6][C:27]([C:23]1[N:18]2[CH:19]=[C:20]([CH3:22])[CH:21]=[C:16]([O:15][CH2:14][C:13]3[C:30]([F:34])=[CH:31][CH:32]=[CH:33][C:12]=3[F:11])[C:17]2=[N:25][C:24]=1[CH3:26])=[O:28]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 73236151HCID 73236151, compound2×HCID 867178848-[(2,6-Difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 90114467HCID 90114467, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22392675Trifluoroacetic acid waterSolvent

Procedure

118 mg (0.66 mmol) of rac-3,3,3-trifluoro-2-methylpropane-1,2-diamine hydrochloride Example 246A were added to 200 mg (0.60 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid Example 21A, 203 mg (0.63 mmol) of TBTU and 0.27 ml (2.41 mmol) of 4-methylmorpholine in DMF (2.1 ml), and the reaction mixture was stirred at RT overnight. 50 mg (0.28 mmol) of rac-3,3,3-trifluoro-2-methylpropane-1,2-diamine hydrochloride Example 246A were added to the reaction mixture, and stirring was continued at RT overnight. The mixture was diluted with water/TFA and purified by preparative 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 219 mg (79% of theory, purity 99%) of the target compound.

Workup

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

Sources & evidence

ORD record
ord-3213b702de0141ecbcf0049fa7781cf8
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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