4-Methylmorpholine → HCID 90113892, compound

HRID 2275906Notes

Reaction equation

HRID 2275906 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]([OH:19])=O)=[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.[CH:56]1([C:59]([NH2:63])([CH3:62])[CH2:60][NH2:61])[CH2:58][CH2:57]1>CN(C=O)C.O.C(O)(C(F)(F)F)=O>[NH2:63][C:59]([CH:56]1[CH2:58][CH2:57]1)([CH3:62])[CH2:60][NH:61][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:2]([F:1])=[CH:23][CH:22]=[CH:21][C:20]=3[F:24])[C:7]2=[N:15][C:14]=1[CH3:16])=[O:19]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 54592674HCID 54592674, compound2×HCID 867178848-[(2,6-Difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 90113892HCID 90113892, compound

Reagents, catalysts & solvents 2

HCID 22392675Trifluoroacetic acid waterCatalystHCID 6228DimethylformamideSolvent

Procedure

160 mg (0.48 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid Example 21A, 162 mg (0.51 mmol) of TBTU and 292 mg (2.89 mmol) of 4-methylmorpholine were initially charged in DMF (1.7 ml), and 99 mg (0.53 mmol) of rac-2-cyclopropylpropane-1,2-diamine dihydrochloride were added at 0° C. The reaction mixture was allowed to warm to room temperature and then stirred at RT overnight. Another 50 mg (0.27 mmol) of 2-cyclopropylpropane-1,2-diamine dihydrochloride and 49 mg (0.48 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 prep. RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA). 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 156 mg (76% of theory) of the target compound.

Workup

  1. stirringthe mixture was stirred at RT for 1.5 h
  2. custompurified by prep
  3. additionRP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA)
  4. concentrationThe product fractions were 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-4ed54c054ee849d18ba1bd83826a5f7b
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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