Diisopropylethylamine → HCID 86670404, compound

HRID 1972606Notes

Reaction equation

HRID 1972606 reaction equation
[CH3:1][CH:2]([CH3:23])[CH2:3][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].Cl[C:25]1[N:30]=[CH:29][C:28]([C:31]([OH:40])([C:36]([F:39])([F:38])[F:37])[C:32]([F:35])([F:34])[F:33])=[CH:27][N:26]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[CH3:1][CH:2]([CH3:23])[CH2:3][N:4]([CH2:9][C@@H:10]1[N:15]([C:25]2[N:26]=[CH:27][C:28]([C:31]([OH:40])([C:32]([F:33])([F:34])[F:35])[C:36]([F:38])([F:39])[F:37])=[CH:29][N:30]=2)[CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:11]1)[S:5]([CH3:8])(=[O:6])=[O:7]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 66582547HCID 66582547, compoundHCID 866703482-(2-Chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol2×

Product 1

HCID 86670404HCID 86670404, compoundYield 77.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 20-mL vial was charged with tert-butyl (3R)-3-(((2-methylpropyl)(methylsulfonyl)amino)methyl)-1-piperazinecarboxylate (0.498 g, 1.42 mmol, step 1), 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (0.479 g, 1.71 mmol, Intermediate D), DIPEA (0.75 mL, 4.3 mmol) and 1,4-dioxane (5 mL). The mixture was heated at 100° C. for 12 h and then cooled to room temperature and partitioned between water (50 mL) and EtOAc (40 mL). The aqueous phase was extracted with EtOAc (40 mL) and the combined organic extracts were 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-(((2-methylpropyl)(methylsulfonyl)amino)methyl)-4-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-1-piperazinecarboxylate (0.655 g) as a light-yellow foam.

Workup

  1. temperaturecooled to room temperature
  2. custompartitioned between water (50 mL) and EtOAc (40 mL)
  3. extractionThe aqueous phase was extracted with EtOAc (40 mL)
  4. washthe combined organic extracts were washed with saturated aqueous NaCl (60 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by column chromatography (50 g of silica gel, 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6d763b580c74439cbb51014e7a195883
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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