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

HRID 2233915Notes

Reaction equation

HRID 2233915 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[CH:26]=[C:27]([C:31]([OH:33])=O)[NH:28][C:29]=1[CH3:30].Cl.[NH2:35][CH:36]1[CH2:41][CH2:40][N:39]([C:42]2[CH:43]=[C:44]([CH:48]=[C:49]([Cl:51])[N:50]=2)[C:45]([NH2:47])=[O:46])[CH2:38][CH2:37]1>CN(C=O)C>[Cl:51][C:49]1[CH:48]=[C:44]([CH:43]=[C:42]([N:39]2[CH2:40][CH2:41][CH:36]([NH:35][C:31]([C:27]3[NH:28][C:29]([CH3:30])=[C:25]([Cl:24])[CH:26]=3)=[O:33])[CH2:37][CH2:38]2)[N:50]=1)[C:45]([NH2:47])=[O:46]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 251376814-Chloro-5-methyl-1H-pyrrole-2-carboxylic acid2×HCID 86608255HCID 86608255, compound2×

Product 1

HCID 574012402-Chloro-6-(4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)isonicotinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Diisopropylethylamine (0.34 ml, 2.0 mmol), EDC (0.121 g, 0.63 mmol) and HOAT (0.086 g, 0.63 mmol) were added to a stirred solution of 4-chloro-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 8, 0.1 g, 0.63 mmol) in DMF (2 ml) at room temperature. The resultant solution was stirred for 15 mins then a solution of 2-(4-aminopiperidin-1-yl)-6-chloroisonicotinamide hydrochloride (Intermediate 70, 0.19 g, 0.75 mmol) in 3 ml of DMF was added. The reaction was concentrated after 2 hours and the residue was partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc (×2), the combined organic layers were washed with 1 N HCl, water and brine, then dried over magnesium sulfate and concentrated under vacuum. The residue was purified by reverse phase chromatography (water/acetonitrile gradient, 20-95%) to give the title product as a white solid.

Workup

  1. concentrationThe reaction was concentrated after 2 hours
  2. customthe residue was partitioned between water and EtOAc
  3. extractionThe aqueous layer was extracted with EtOAc (×2)
  4. washthe combined organic layers were washed with 1 N HCl, water and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by reverse phase chromatography (water/acetonitrile gradient, 20-95%)

Sources & evidence

ORD record
ord-a881123af776447db6ecb1f9197fa77a
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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