1,2-Dichloroethane → 2-Chloro-6-(4-{[(4-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)isonicotinamide

HRID 2233918Notes

Reaction equation

HRID 2233918 reaction equation
C(N(C(C)C)CC)(C)C.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.[C:24]([C:26]1[CH:27]=[C:28]([C:32]([OH:34])=O)[NH:29][C:30]=1[CH3:31])#[N:25].Cl.[NH2:36][CH:37]1[CH2:42][CH2:41][N:40]([C:43]2[CH:44]=[C:45]([CH:49]=[C:50]([Cl:52])[N:51]=2)[C:46]([NH2:48])=[O:47])[CH2:39][CH2:38]1>CN(C=O)C>[Cl:52][C:50]1[CH:49]=[C:45]([CH:44]=[C:43]([N:40]2[CH2:41][CH2:42][CH:37]([NH:36][C:32]([C:28]3[NH:29][C:30]([CH3:31])=[C:26]([C:24]#[N:25])[CH:27]=3)=[O:34])[CH2:38][CH2:39]2)[N:51]=1)[C:46]([NH2:48])=[O:47]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 598647364-Cyano-5-methyl-1H-pyrrole-2-carboxylic acid2×HCID 866082552-(4-Aminopiperidin-1-yl)-6-chloroisonicotinamide hydrochloride2×

Product 1

HCID 573960072-Chloro-6-(4-{[(4-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)isonicotinamideYield 7.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Diisopropylethylamine (0.1 ml, 0.56 mmol), EDC (0.09 g, 0.46 mmol) and HOAT (0.064 g, 0.46 mmol) were added to a stirred solution of 4-cyano-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 13, 0.07 g, 0.47 mmol) in DMF (1.5 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, 0.16 g, 0.56 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 (13 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-f75de6db6527438f9832fa3ac09081ec
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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