4-Methylmorpholine → HCID 86717989, compound

HRID 2275904Notes

Reaction equation

HRID 2275904 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:13]([C:17](O)=[O:18])=[C:14]([CH3:16])[N:15]=2)[CH:9]=[C:10]([CH3:12])[CH:11]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1.Cl.Cl.[C:56]([NH:60][CH2:61][CH2:62][NH2:63])([CH3:59])([CH3:58])[CH3:57]>CN(C=O)C.O.C(O)(C(F)(F)F)=O>[C:56]([NH:60][CH2:61][CH2:62][NH:63][C:17]([C:13]1[N:8]2[CH:9]=[C:10]([CH3:12])[CH:11]=[C:6]([O:5][CH2:4][C:3]3[C:20]([F:24])=[CH:21][CH:22]=[CH:23][C:2]=3[F:1])[C:7]2=[N:15][C:14]=1[CH3:16])=[O:18])([CH3:59])([CH3:58])[CH3:57]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 50988286HCID 50988286, compound2×HCID 867178848-[(2,6-Difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 86717989HCID 86717989, compound

Reagents, catalysts & solvents 2

HCID 22392675Trifluoroacetic acid waterCatalystHCID 6228DimethylformamideSolvent

Procedure

70 mg (0.21 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid Example 21A, 71 mg (0.22 mmol) of TBTU and 128 mg (1.26 mmol) of 4-methylmorpholine were initially charged in DMF (0.74 ml), 44 mg (0.23 mmol) of N-tert-butylethane-1,2-diamine dihydrochloride were added and the reaction mixture was stirred at RT overnight. Another 22 mg (0.12 mmol) of N-tert-butylethane-1,2-diamine dihydrochloride and 21 mg (0.21 mmol) of 4-methylmorpholine were added, and the mixture was stirred at RT for 1.5 h. The mixture was diluted with a few drops of water/TFA and purified by preparative RP-HPLC (acetonitrile/water with addition of 0.1% TFA), and the product fractions were 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 78 mg (86% of theory, purity 96%) of the target compound.

Workup

  1. stirringthe mixture was stirred at RT for 1.5 h
  2. custompurified by preparative RP-HPLC (acetonitrile/water with addition of 0.1% TFA)
  3. concentrationthe product fractions were 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-8478f60d58a64230b4c9d3df3351b82e
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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