Diisopropylethylamine → 2-(4-((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

HRID 1972592Notes

Reaction equation

HRID 1972592 reaction equation
[N+:1]([C:4]1[S:8][C:7]([S:9]([N:12]2[CH2:17][CH2:16][NH:15][C@@H:14]([CH2:18][N:19]3[CH2:24][CH2:23][O:22][CH2:21][C@@H:20]3[CH3:25])[CH2:13]2)(=[O:11])=[O:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].ClC1N=[CH:31][C:30]([C:33]([OH:42])([C:38]([F:41])([F:40])[F:39])[C:34]([F:37])([F:36])[F:35])=[CH:29]N=1.CCN(C(C)C)[CH:46]([CH3:48])[CH3:47]>O1CCOCC1>[N+:1]([C:4]1[S:8][C:7]([S:9]([N:12]2[CH2:17][CH2:16][N:15]([C:46]3[CH:48]=[CH:31][C:30]([C:33]([OH:42])([C:38]([F:41])([F:40])[F:39])[C:34]([F:37])([F:36])[F:35])=[CH:29][CH:47]=3)[C@@H:14]([CH2:18][N:19]3[CH2:24][CH2:23][O:22][CH2:21][C@@H:20]3[CH3:25])[CH2:13]2)(=[O:10])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 66582427(3S)-4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-methylmorpholineHCID 866703482-(2-Chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol2×

Product 1

HCID 866704002-(4-((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanolYield 72.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 20-mL vial was charged with (3S)-4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-methylmorpholine (0.797 g, 2.04 mmol, step 4), (2-chloro-5-pyrimidinyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.859 g, 3.06 mmol, Intermediate D), DIPEA (1.10 mL, 6.30 mmol) and 1,4-dioxane (10 mL). The vial was sealed and heated at 100° C. for 12 h. The reaction mixture was allowed to cool to room temperature and then partitioned between water (30 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (40 mL). The combined organic phases were washed with saturated aqueous NaCl (50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (50 g of silica gel, 0 to 50% EtOAc in hexanes) to afford 2-(4-((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.936 g) as a tan solid.

Workup

  1. customThe vial was sealed
  2. temperatureto cool to room temperature
  3. custompartitioned between water (30 mL) and EtOAc (20 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (40 mL)
  5. washThe combined organic phases were washed with saturated aqueous NaCl (50 mL)
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography (50 g of silica gel, 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ce385dbe78764811b12037597b86b4c7
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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