1-(4-Isothiocyanatophenyl)ethanone → 1-(4-{[5-(butylamino)-3-(3-piperidin-1-ylpropyl)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)ethanone

HRID 1727041Notes

Reaction equation

HRID 1727041 reaction equation
[CH2:1]([NH:5][C:6]1[N:11]=[C:10]([NH:12][CH2:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[C:9]([N+:22]([O-])=O)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].[C:25]([C:28]1[CH:33]=[CH:32][C:31]([N:34]=[C:35]=S)=[CH:30][CH:29]=1)(=[O:27])[CH3:26]>C(OCC)(=O)C.C(O)C.[Pd].O1CCCC1>[CH2:1]([NH:5][C:6]1[N:11]=[C:10]2[N:12]([CH2:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[C:35]([NH:34][C:31]3[CH:32]=[CH:33][C:28]([C:25](=[O:27])[CH3:26])=[CH:29][CH:30]=3)=[N:22][C:9]2=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 2

HCID 2427791-(4-Isothiocyanatophenyl)ethanoneHCID 86606889N6-butyl-3-nitro-N2-(3-piperidin-1-ylpropyl)pyridine-2,6-diamine

Product 1

HCID 575662601-(4-{[5-(butylamino)-3-(3-piperidin-1-ylpropyl)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)ethanoneYield 34.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 21584252Ethanol ethylacetateSolvent

Conditions

Temperature
20 °C

Procedure

N6-butyl-3-nitro-N2-(3-piperidin-1-ylpropyl)pyridine-2,6-diamine (500 mg) in solution in a mixture of ethyl acetate/ethanol 3:1 (10 ml), and 10% palladium on carbon (50 mg) are introduced into an autoclave. After stirring for 3 hours under a hydrogen atmosphere (3 bar) at a temperature of approximately 20° C., the mixture is filtered on celite in a flask containing a solution of 4-acetylphenyl-isothiocyanate (270 mg, 1 eq) in tetrahydrofuran (10 ml). N-cyclohexylcarbodiimide-N-methyl-polystyrene resin (acquired from Novabiochem; load 1.9 mmol/g; 2.63 g, 3 eq) is added to the filtrate thus obtained. The mixture is heated to reflux for 15 hours, cooled down to ambient temperature then filtered on frit and the filtrate is concentrated under reduced pressure at 40° C. Purification of the residue by flash chromatography on silica gel (eluent: 100% dichloromethane to dichloromethane/methanol 9:1) produces the expected compound (230 mg; 34% yield).

Workup

  1. additionare introduced into an autoclave
  2. filtrationthe mixture is filtered on celite in a flask
  3. customthus obtained
  4. temperatureThe mixture is heated
  5. temperatureto reflux for 15 hours
  6. temperaturecooled down to ambient temperature
  7. filtrationthen filtered on frit
  8. concentrationthe filtrate is concentrated under reduced pressure at 40° C
  9. customPurification of the residue by flash chromatography on silica gel (eluent: 100% dichloromethane to dichloromethane/methanol 9:1)

Sources & evidence

ORD record
ord-380ba71b9e254d24af9b2cc1ec6a2ab1
Source dataset
uspto-grants-2009_02
Patent number
US07495009B2

Reaction notes

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