N,N'-Dimethylethylenediamine → HCID 56932994, compound

HRID 1972649Notes

Reaction equation

HRID 1972649 reaction equation
[CH3:1][CH:2]([CH3:36])[CH2:3][S:4]([NH:7][CH2:8][C@H:9]1[CH2:14][N:13]([S:15]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)(=[O:17])=[O:16])[CH2:12][CH2:11][N:10]1[C:23]1[CH:28]=[CH:27][C:26]([C:29]([OH:35])([CH3:34])[C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=1)(=[O:6])=[O:5].I[C:38]1[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=1.CNCCNC.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.[Cu]I.O>[CH3:1][CH:2]([CH3:36])[CH2:3][S:4]([N:7]([C:38]1[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=1)[CH2:8][C@H:9]1[CH2:14][N:13]([S:15]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)(=[O:16])=[O:17])[CH2:12][CH2:11][N:10]1[C:23]1[CH:28]=[CH:27][C:26]([C:29]([OH:35])([CH3:34])[C:30]([F:32])([F:31])[F:33])=[CH:25][CH:24]=1)(=[O:6])=[O:5]

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 707143-IodopyridineHCID 665824452-methyl-N-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-1-propanesulfonamide

Product 1

HCID 56932994HCID 56932994, compoundYield 10.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-methyl-N-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-1-propanesulfonamide (0.130 g, 0.228 mmol) in DMF (3.0 mL) was added 3-iodopyridine (0.094 g, 0.46 mmol, Sigma-Aldrich, St. Louis, Mo.), N,N′-dimethylethylenediamine (0.020 mL, 0.18 mmol, Sigma-Aldrich, St. Louis, Mo.), copper(i) iodide (0.022 g, 0.11 mmol, Sigma-Aldrich, St. Louis, Mo.), cesium carbonate (0.223 g, 0.685 mmol, Sigma-Aldrich, St. Louis, Mo.), and water (0.300 mL). The resulting mixture was heated at 120° C. under N2 for 5 days. The reaction mixture was filtered through the Celite® (diatomaceous earth) and the filtrate was concentrated. The residue was purified by column chromatography (24 g of silica, 1% to 5% (2M NH3 in MeOH) in DCM) to afford 2-methyl-N-3-pyridinyl-N-(((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-1-propanesulfonamide (15 mg) as a mixture of 2 isomers.

Workup

  1. filtrationThe reaction mixture was filtered through the Celite® (diatomaceous earth)
  2. concentrationthe filtrate was concentrated
  3. customThe residue was purified by column chromatography (24 g of silica, 1% to 5% (2M NH3 in MeOH) in DCM)

Sources & evidence

ORD record
ord-9de3542fa27446dd9884ce556e760982
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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