Diisopropylethylamine → HCID 86670405, compound

HRID 1972611Notes

Reaction equation

HRID 1972611 reaction equation
[CH3:1][CH:2]([N:4]([CH2:9][C@@H:10]1[NH:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]1)[S:5]([CH3:8])(=[O:7])=[O:6])[CH3:3].Cl[C:24]1[N:29]=[CH:28][C:27]([C:30]([OH:39])([C:35]([F:38])([F:37])[F:36])[C:31]([F:34])([F:33])[F:32])=[CH:26][N:25]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[CH3:3][CH:2]([N:4]([CH2:9][C@@H:10]1[N:15]([C:24]2[N:25]=[CH:26][C:27]([C:30]([OH:39])([C:31]([F:32])([F:33])[F:34])[C:35]([F:37])([F:38])[F:36])=[CH:28][N:29]=2)[CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:11]1)[S:5]([CH3:8])(=[O:6])=[O:7])[CH3:1]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 66583235HCID 66583235, compoundHCID 866703482-(2-Chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol4×

Product 1

HCID 86670405HCID 86670405, compoundYield 83.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 20-mL vial was charged with tert-butyl (3R)-3-(((1-methylethyl)(methylsulfonyl)amino)methyl)-1-piperazinecarboxylate (0.315 g, 0.939 mmol, step 1), 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (0.287 g, 1.02 mmol, Intermediate D), DIPEA (0.492 mL, 2.82 mmol) and 1,4-dioxane (5 mL). The vial was sealed and heated at 100° C. for 12 h. The reaction mixture was allowed to cool to room temperature and additional 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (0.082 g, 0.29 mmol, Intermediate D) was added. The mixture was heated at 100° C. for an additional 12 h. After allowing the reaction to cool to room temperature, the mixture was partitioned between water (50 mL) and EtOAc (40 mL). The aqueous phase was extracted with EtOAc (40 mL). The combined organic extracts was washed with saturated aqueous NaCl (60 mL), 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 tert-butyl (3R)-3-(((1-methylethyl)(methylsulfonyl)amino)methyl)-4-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-1-piperazinecarboxylate (0.455 g) as a light yellow foam.

Workup

  1. customThe vial was sealed
  2. temperatureto cool to room temperature
  3. temperatureThe mixture was heated at 100° C. for an additional 12 h
  4. customthe reaction
  5. temperatureto cool to room temperature
  6. customthe mixture was partitioned between water (50 mL) and EtOAc (40 mL)
  7. extractionThe aqueous phase was extracted with EtOAc (40 mL)
  8. washThe combined organic extracts was washed with saturated aqueous NaCl (60 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude product was purified by column chromatography (50 g of silica gel, 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9031997bb51e4c7198648da971329ab4
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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