1,2-Dichloroethane → 2-(4-{[(3,4-Dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-1,3-thiazole-5-carboxamide

HRID 2233926Notes

Reaction equation

HRID 2233926 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]([NH:34][CH:35]1[CH2:40][CH2:39][N:38]([C:41]2C=CN=[C:43](S(C)=O)[N:42]=2)[CH2:37][CH2:36]1)=[O:33].Cl.NC1CCN(C2[S:59][C:60]([C:63]([NH2:65])=[O:64])=CN=2)CC1>CN(C=O)C>[Cl:24][C:25]1[C:29]([Cl:30])=[C:28]([CH3:31])[NH:27][C:26]=1[C:32]([NH:34][CH:35]1[CH2:36][CH2:37][N:38]([C:41]2[S:59][C:60]([C:63]([NH2:65])=[O:64])=[CH:43][N:42]=2)[CH2:39][CH2:40]1)=[O:33]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 68579945HCID 68579945, compound2×HCID 68582668HCID 68582668, compound2×

Product 1

HCID 685799292-(4-{[(3,4-Dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-1,3-thiazole-5-carboxamideYield 24.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Diisopropylethylamine (0.19 ml, 1.12 mmol), EDC (0.098 g, 0.51 mmol) and HOAT (0.070 g, 0.51 mmol) were added to a stirred solution of 3,4-dichloro-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 3, 0.1 g, 0.51 mmol) in DMF (1.5 ml) at room temperature. The resultant solution was stirred for 30 mins and 2-(4-aminopiperidin-1-yl)-1,3-thiazole-5-carboxamide hydrochloride (Intermediate 81; 0.163 g, 0.62 mmol) was added. The reaction was stirred at room temperature overnight under nitrogen. 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 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 (water/acetonitrile gradient, 20-95%) to give the desired product as a white solid (50 mg).

Workup

  1. stirringThe reaction was stirred overnight
  2. concentrationconcentrated under vacuum
  3. customthe residue was partitioned between water and EtOAc
  4. extractionThe aqueous layer was extracted with EtOAc
  5. washthe combined organic extracts were washed with 1 N HCl, water and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by reverse phase chromatography (water/acetonitrile gradient, 20-95%)

Sources & evidence

ORD record
ord-3757b77bba1f4c02a55bc45c14e36d2d
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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