Diisopropylethylamine → HCID 86670407, compound

HRID 1972617Notes

Reaction equation

HRID 1972617 reaction equation
[CH3:1][S:2]([N:5]([CH2:12][C@@H:13]1[NH:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=[O:4])=[O:3].Cl[C:27]1[N:32]=[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:28]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[CH3:1][S:2]([N:5]([CH2:12][C@@H:13]1[N:18]([C:27]2[N:28]=[CH:29][C:30]([C:33]([OH:42])([C:34]([F:35])([F:36])[F:37])[C:38]([F:40])([F:41])[F:39])=[CH:31][N:32]=2)[CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)(=[O:3])=[O:4]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 70659853HCID 70659853, compoundHCID 866703482-(2-Chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol2×

Product 1

HCID 86670407HCID 86670407, compoundYield 65.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 20-mL vial was charged with tert-butyl (3R)-3-(((methylsulfonyl)(phenyl)amino)methyl)-1-piperazinecarboxylate (0.425 g, 1.15 mmol, step 4), 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (0.411 g, 1.47 mmol, Intermediate D), DIPEA (0.602 mL, 3.45 mmol) and 1,4-dioxane (5 mL). The vial was sealed and the reaction mixture was heated at 100° C. for 20 h. The reaction mixture was allowed to cool to room temperature and partitioned between water (30 mL) and EtOAc (30 mL). The aqueous phase was extracted with EtOAc (2×30 mL). The combined organic phases were washed with saturated aqueous NaCl (50 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-(((methylsulfonyl)(phenyl)amino)methyl)-4-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-1-piperazinecarboxylate (0.464 g) as a light-brown solid.

Workup

  1. customThe vial was sealed
  2. temperatureto cool to room temperature
  3. custompartitioned between water (30 mL) and EtOAc (30 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (2×30 mL)
  5. washThe combined organic phases were washed with saturated aqueous NaCl (50 mL)
  6. dry with materialdried 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-d2fa6ee0dc7e43c5bd69d71675b5aaa0
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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