1,2-Dichloroethane → 2-Chloro-6-(4-{[(3,4-Dichloro-5-Methyl-1h-Pyrrol-2-Yl)carbonyl]amino}piperidin-1-Yl)pyridine-4-Carboxamide

HRID 2233917Notes

Reaction equation

HRID 2233917 reaction equation
C(N(C(C)C)CC)(C)C.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.[Cl:24][C:25]1[C:29]([Cl:30])=[C:28]([CH3:31])[NH:27][C:26]=1[C:32](NC1CCN(C2C=CN=C(S(C)=O)N=2)CC1)=[O:33].Cl.[NH2:51][CH:52]1[CH2:57][CH2:56][N:55]([C:58]2[CH:59]=[C:60]([CH:64]=[C:65]([Cl:67])[N:66]=2)[C:61]([NH2:63])=[O:62])[CH2:54][CH2:53]1>CN(C=O)C>[Cl:67][C:65]1[CH:64]=[C:60]([CH:59]=[C:58]([N:55]2[CH2:54][CH2:53][CH:52]([NH:51][C:32]([C:26]3[NH:27][C:28]([CH3:31])=[C:29]([Cl:30])[C:25]=3[Cl:24])=[O:33])[CH2:57][CH2:56]2)[N:66]=1)[C:61]([NH2:63])=[O:62]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 68582668HCID 68582668, compound2×HCID 866082552-(4-Aminopiperidin-1-yl)-6-chloroisonicotinamide hydrochloride2×

Product 1

HCID 112125912-Chloro-6-(4-{[(3,4-Dichloro-5-Methyl-1h-Pyrrol-2-Yl)carbonyl]amino}piperidin-1-Yl)pyridine-4-CarboxamideYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Diisopropylethylamine (0.063 ml, 0.37 mmol), EDC (0.095 g, 0.31 mmol) and HOAT (0.042 g, 0.31 mmol) were added to a stirred solution of 3,4-dichloro-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 3, 0.060 g, 0.31 mmol) in DMF (1.0 ml) at room temperature. The resultant solution was stirred for 30 mins and a solution of 2-(4-aminopiperidin-1-yl)-6-chloroisonicotinamide hydrochloride (Intermediate 70, 0.096 g, 0.37 mmol) in 1 ml of DMF was added. The reaction was stirred overnight, then concentrated under vacuum and the residue was partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc (×2) and the combined organic extracts were washed with 1 N HCl, water and brine, dried over MgSO4 and concentrated under vacuum. The residue was purified by reverse phase chromatography to give the desired product as a white solid (40 mg).

Workup

  1. concentrationconcentrated under vacuum
  2. customthe residue was partitioned between water and EtOAc
  3. extractionThe aqueous layer was extracted with EtOAc (×2)
  4. washthe combined organic extracts were washed with 1 N HCl, water and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-ac78fc698d2d43eab0d8ac868106da83
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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