N,N'-Dimethylethylenediamine → HCID 56932994, compound

HRID 1972586Notes

Reaction equation

HRID 1972586 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-Iodopyridine2×HCID 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 0%

Reagents, catalysts & solvents 3

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

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, Example 210) in DMF (3.0 mL) was added 3-iodopyridine (0.094 g, 0.46 mmol, Aldrich, St. Louis, Mo.), N,N′-dimethylethylenediamine (0.020 mL, 0.18 mmol, Aldrich, St. Louis, Mo.), CuI (0.015 mg, 0.21 mmol, Aldrich, St. Louis, Mo.), cesium carbonate (0.22 g, 0.69 mmol), and water (0.30 mL). The resulting mixture was heated at 120° C. for 14 d, with additional aliquots of 3-iodopyridine (50 mg, 0.23 mmol) being added on 2nd and 5th day. The reaction mixture was then filtered and the filtrate was concentrated. The crude product was purified by column chromatography (24 g of silica gel, 1 to 5% 2M NH3 in MeOH in CH2Cl2) 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 (0.015 mg) as a mixture of two isomers.

Workup

  1. additionbeing added on 2nd and 5th day
  2. filtrationThe reaction mixture was then filtered
  3. concentrationthe filtrate was concentrated
  4. customThe crude product was purified by column chromatography (24 g of silica gel, 1 to 5% 2M NH3 in MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-906143e6be624c01a65ad300eb55a83b
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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