Diisopropylethylamine → HCID 68107525, compound

HRID 2403623Notes

Reaction equation

HRID 2403623 reaction equation
[ClH:1].[Cl:2][C:3]1[CH:11]=[C:10]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=[O:6].[Cl:18][C:19]1[N:24]=[CH:23][C:22]([C:25]2[CH:26]=[C:27]([CH:42]=[CH:43][CH:44]=2)[CH2:28][N:29]([CH3:41])[C:30](=[O:40])[CH2:31][NH:32]C(=O)OC(C)(C)C)=[CH:21][N:20]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[ClH:2].[ClH:18].[Cl:1][C:11]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N:12]1[CH2:17][CH2:16][N:15]([C:19]2[N:20]=[CH:21][C:22]([C:25]3[CH:44]=[CH:43][CH:42]=[C:27]([CH2:28][N:29]([C:30](=[O:40])[CH2:31][NH2:32])[CH3:41])[CH:26]=3)=[CH:23][N:24]=2)[CH2:14][CH2:13]1)[C:5]([OH:7])=[O:6]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86667972HCID 86667972, compoundHCID 86762597HCID 86762597, compound

Product 1

HCID 68107525HCID 68107525, compoundYield 26.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

3 chloro-4-(piperazin-1-yl)benzoic acid hydrochloride (142 mg) was suspended in DMF (3 ml), and tert-butyl (2-{[3-(2-chloropyrimidin-5-yl)benzyl](methyl)amino}-2-oxoethyl)carbamate (190 mg) and DIPEA (371 mg) were added thereto, followed by stirring at 130° C. overnight. The reaction mixture was concentrated under reduced pressure, and then a saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with CHCl3. The organic layer was dried over Na2SO4 and the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH). The product was dissolved in dioxane, and 4 M hydrogen chloride/dioxane (1 ml) was added thereto, followed by stirring at room temperature overnight. The precipitated solid was collected by filtration to obtain 3-chloro-4-{4-[5-(3-{[glycyl(methyl)amino)methyl}phenyl)pyrimidin-2-yl]piperazin-1-yl}benzoic acid dihydrochloride (72 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiona saturated aqueous sodium hydrogen carbonate solution was added
  3. extractionfollowed by extraction with CHCl3
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationthe solvent was concentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)
  7. dissolutionThe product was dissolved in dioxane
  8. addition4 M hydrogen chloride/dioxane (1 ml) was added
  9. stirringby stirring at room temperature overnight
  10. filtrationThe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-9b9e10a1f94745678d395800bf0626a3
Source dataset
uspto-grants-2014_08
Patent number
US08802679B2

Reaction notes

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