Sarcosine → HCID 66582435, compound

HRID 1972585Notes

Reaction equation

HRID 1972585 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].CNCC(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].I[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>[Cu]I.CN(C=O)C>[CH3:1][CH:2]([CH3:36])[CH2:3][S:4]([N:7]([C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=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

7

Reactant 4

HCID 1088SarcosineHCID 11575IodobenzeneHCID 62657Potassium Phosphate, TribasicHCID 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 66582435HCID 66582435, compoundYield 35.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a flame-dry 50-mL round-bottomed flask was added 2-methyl-N-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-1-propanesulfonamide (0.100 g, 0.176 mmol, Example 210), N-methylglycine (3.0 mg, 0.040 mmol, Aldrich, St. Louis, Mo.), CuI (0.02 g, 0.09 mmol, Aldrich, St. Louis, Mo.), and potassium phosphate (0.08 g, 0.37 mmol, Aldrich, St. Louis, Mo.). After the mixture was stirred for 10 min, iodobenzene (0.030 g, 0.14 mmol, Aldrich, St. Louis, Mo.) and DMF (3.0 mL) were added. The resulting mixture was heated at 110° C. for 24 h. Additional CuI was added (7.0 mg, 0.035 mmol) and the reaction was heated at 110° C. for an additional 6 d. The reaction mixture was allowed to cool to room temperature and filtered through a pad of Celite® (diatomaceous earth). The filtrate was concentrated and the crude product was purified by column chromatography (24 g of silica gel, 20 to 40% EtOAc in hexanes) to afford 2-methyl-N-phenyl-N-(((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-1-propanesulfonamide (0.032 g) as a mixture of two isomers:

Workup

  1. temperaturethe reaction was heated at 110° C. for an additional 6 d
  2. temperatureto cool to room temperature
  3. filtrationfiltered through a pad of Celite® (diatomaceous earth)
  4. concentrationThe filtrate was concentrated
  5. customthe crude product was purified by column chromatography (24 g of silica gel, 20 to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1644fa67cbb246dca58dc42db2f4c684
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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