4-Methylmorpholine → HCID 90113925, compound

HRID 2275901Notes

Reaction equation

HRID 2275901 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1.[CH3:30][C:31]([NH2:37])([CH2:34][CH2:35][CH3:36])[CH2:32][NH2:33].[Cl:38][C:39]1[CH:40]=[C:41]([O:52][CH2:53][C:54]2[C:59]([F:60])=[CH:58][CH:57]=[CH:56][C:55]=2[F:61])[C:42]2[N:43]([C:45]([C:49](O)=[O:50])=[C:46]([CH3:48])[N:47]=2)[CH:44]=1>CN(C=O)C.O.C(O)(C(F)(F)F)=O>[NH2:37][C:31]([CH3:30])([CH2:34][CH2:35][CH3:36])[CH2:32][NH:33][C:49]([C:45]1[N:43]2[CH:44]=[C:39]([Cl:38])[CH:40]=[C:41]([O:52][CH2:53][C:54]3[C:55]([F:61])=[CH:56][CH:57]=[CH:58][C:59]=3[F:60])[C:42]2=[N:47][C:46]=1[CH3:48])=[O:50]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11170953100868-68-62×HCID 867178796-Chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 90113925HCID 90113925, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22392675Trifluoroacetic acid waterSolvent

Procedure

191 mg (0.62 mmol) of TBTU and 0.25 ml (2.27 mmol) of 4-methylmorpholine and 72 mg (0.62 mmol) of rac-2-methylpentane-1,2-diamine were added to 200 mg (0.57 mmol) of 6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 16A in DMF (2.0 ml), and the reaction mixture was stirred at RT overnight. 36 mg (0.31 mmol) of rac-2-methylpentane-1,2-diamine and 0.06 ml (0.57 mmol) of 4-methylmorpholine were then added, 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. The residue was purified by silica gel chromatography (dichloromethane/methanol: 10:1, then dichloromethane/2N ammonia in methanol 20:1). This gave 189 mg (73% 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
  10. customThe residue was purified by silica gel chromatography (dichloromethane/methanol

Sources & evidence

ORD record
ord-58837983373e41c7acc3fb3307997e4c
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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