Diisopropylethylamine → HCID 56932828, compound

HRID 1972584Notes

Reaction equation

HRID 1972584 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][N:15]([S:18]([C:21]3[S:22][CH:23]=[CH:24][CH:25]=3)(=[O:20])=[O:19])[CH2:14][C@@H:13]2[CH2:26][NH:27][CH:28]([CH3:30])[CH3:29])=[CH:8][CH:7]=1)([OH:5])[CH3:4].CCN(C(C)C)C(C)C.[CH3:42][N:43]([CH3:48])[S:44](Cl)(=[O:46])=[O:45]>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH3:42][N:43]([CH3:48])[S:44]([N:27]([CH:28]([CH3:29])[CH3:30])[CH2:26][C@H:13]1[CH2:14][N:15]([S:18]([C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)(=[O:20])=[O:19])[CH2:16][CH2:17][N:12]1[C:9]1[CH:8]=[CH:7][C:6]([C:3]([OH:5])([CH3:4])[C:2]([F:1])([F:31])[F:32])=[CH:11][CH:10]=1)(=[O:46])=[O:45]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 83372Dimethylsulphamoyl chlorideHCID 66582708HCID 66582708, compound

Product 1

HCID 56932828HCID 56932828, compoundYield 8.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1,1,1-trifluoro-2-(4-((2S)-2-(((1-methylethyl)amino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (0.100 g, 0.203 mmol, Example 195, Step 1) in pyridine (3.0 mL) was added 4-dimethylaminopyridine (5.0 mg, 0.040 mmol), Hünig's base (0.1 mL, 0.6 mmol), and dimethylsulfamoyl chloride (0.05 mL, 0.4 mmol, Aldrich, St. Louis, Mo.). The resulting mixture was heated at 80° C. for 6 h. The reaction mixture was allowed to cool to room temperature and then partitioned between EtOAc (30 mL) and water (20 mL). The aqueous layer was extracted with EtOAc (2×20 mL) and the combined organic extracts were dried over MgSO4, filtered, and concentrated. The crude product was purified by column chromatography (24 g of silica, 10% to 40% EtOAc in hexanes) to afford N,N-dimethyl-N′-(1-methylethyl)-N′-(((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)sulfamide (0.010 g) as a mixture of two isomers:

Workup

  1. temperatureto cool to room temperature
  2. custompartitioned between EtOAc (30 mL) and water (20 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×20 mL)
  4. dry with materialthe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (24 g of silica, 10% to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b3468b759b624d74be3ffdc5d9aa2c70
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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