Diisopropylethylamine → 3-(1-methylethyl)-4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-2-piperazinone

HRID 1972563Notes

Reaction equation

HRID 1972563 reaction equation
[CH3:1][CH:2]([CH:4]1[N:9]([CH2:10][C@H:11]2[CH2:16][N:15]([S:17]([C:20]3[S:21][C:22]([N+:25]([O-:27])=[O:26])=[CH:23][CH:24]=3)(=[O:19])=[O:18])[CH2:14][CH2:13][NH:12]2)[CH2:8][CH2:7][NH:6][C:5]1=[O:28])[CH3:3].Cl[C:30]1[N:35]=[CH:34][C:33]([C:36]([OH:45])([C:41]([F:44])([F:43])[F:42])[C:37]([F:40])([F:39])[F:38])=[CH:32][N:31]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[CH3:3][CH:2]([CH:4]1[N:9]([CH2:10][C@H:11]2[CH2:16][N:15]([S:17]([C:20]3[S:21][C:22]([N+:25]([O-:27])=[O:26])=[CH:23][CH:24]=3)(=[O:19])=[O:18])[CH2:14][CH2:13][N:12]2[C:30]2[N:31]=[CH:32][C:33]([C:36]([OH:45])([C:37]([F:38])([F:39])[F:40])[C:41]([F:43])([F:44])[F:42])=[CH:34][N:35]=2)[CH2:8][CH2:7][NH:6][C:5]1=[O:28])[CH3:1]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 665829503-(1-methylethyl)-4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-2-piperazinoneHCID 866703482-(2-Chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol2×

Product 1

HCID 866703983-(1-methylethyl)-4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-2-piperazinoneYield 55.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a 20-mL vial, 3-(1-methylethyl)-4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-2-piperazinone (262 mg, 0.607 mmol), 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (170 mg, 0.607 mmol, Intermediate D) and Hünig's base (323 μL, 1.852 mmol) were dissolved into dioxane (3.77 mL). The vial was sealed and the reaction mixture was stirred at 100° C. for 12 h. After cooling to room temperature, the mixture was partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc, and the combined organic phases were washed with brine. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (40 to 100% EtOAc in hexanes gradient) to give the title compound (228 mg).

Workup

  1. customThe vial was sealed
  2. temperatureAfter cooling to room temperature
  3. customthe mixture was partitioned between water and EtOAc
  4. extractionThe aqueous phase was extracted with EtOAc
  5. washthe combined organic phases were washed with brine
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified by silica gel chromatography (40 to 100% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-59d698e0437a45238e935286aa32eef5
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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