Methanol → HCID 118022617, compound

HRID 1498875Notes

Reaction equation

HRID 1498875 reaction equation
C([S@]([NH:7][C@:8]([C:20]1[CH:21]=[N:22][C:23]([N:26]2[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]2)=[N:24][CH:25]=1)([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[C:9]([F:12])([F:11])[F:10])=O)(C)(C)C.CO>Cl.O1CCOCC1>[F:12][C:9]([F:10])([F:11])[C@:8]([C:13]1[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=1)([C:20]1[CH:21]=[N:22][C:23]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[N:24][CH:25]=1)[NH2:7]

Participants

5

Reactant 2

HCID 887MethanolHCID 118022207HCID 118022207, compound

Product 1

HCID 118022617HCID 118022617, compoundYield 99.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 4-(5-((S)-1-(((R)-tert-butylsulfinyl)amino)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)pyrimidin-2-yl)piperazine-1-carboxylate (302 mg, 0.540 mmol) was stirred in 4 M HCl in 1,4-dioxane (3 mL)/MeOH (3 mL) at room temperature for 1 hour. The solvent was removed in vacuo and the residue was partitioned between saturated NaHCO3 and EtOAc. The organic phase was extracted a second time with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give (S)-2,2,2-trifluoro-1-(4-fluorophenyl)-1-(2-(piperazin-1-yl)pyrimidin-5-yl)ethanamine (190 mg, 0.535 mmol, 99% yield) with ˜88% e.e. Further purification by chiral SFC gave (S)-2,2,2-trifluoro-1-(4-fluorophenyl)-1-(2-(piperazin-1-yl)pyrimidin-5-yl)ethanamine (123.7 mg, 0.348 mmol, 71.2% yield) with ˜99% e.e.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between saturated NaHCO3 and EtOAc
  3. extractionThe organic phase was extracted a second time with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-20341116057743a8af60f8e6c18125b0
Source dataset
uspto-grants-2015_12
Patent number
US09200002B2

Reaction notes

Loading…