HCID 178458084, compound → HCID 178461774, compound

HRID 1424151Notes

Reaction equation

HRID 1424151 reaction equation
[NH2:1][C:2](=[O:27])[CH:3]([CH3:26])[C@H:4]([NH:18]C(=O)OC(C)(C)C)[C:5]1[NH:9][C:8]2[CH:10]=[CH:11][C:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:13][C:7]=2[N:6]=1>C(Cl)Cl.C(O)(C(F)(F)F)=O>[NH2:18][C@H:4]([C:5]1[NH:9][C:8]2[CH:10]=[CH:11][C:12]([C:14]([CH3:15])([CH3:17])[CH3:16])=[CH:13][C:7]=2[N:6]=1)[C@@H:3]([CH3:26])[C:2]([NH2:1])=[O:27]

Participants

4

Reactant 1

HCID 178458084HCID 178458084, compound

Product 1

HCID 178461774HCID 178461774, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of tert-butyl [(1S)-3-amino-1-(5-tert-butyl-1H-benzimidazol-2-yl)-2-methyl-3-oxopropyl]carbamate (Preparation 29, 3.07 g, 8.2 mmol) in DCM (50 mL) and TFA (10 mL) was stirred at room temperature for 3 hours before concentrating in vacuo. Saturated aqueous NaHCO3 solution (100 mL) was added and the product extracted with 2-MeTHF (4×100 mL). The organic layers were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified using reverse phase column chromatography eluting with 0-40% acetonitrile in water. The resulting solid was dissolved in MeCN (40 mL) at 50° C. and methanol added before allowing the solution to cool. The resulting white precipitate was collected, dried, and further triturated with EtOAc (5 mL) twice to afford a white solid as the desired (2R,3S) diastereomer.

Workup

  1. concentrationbefore concentrating in vacuo
  2. additionSaturated aqueous NaHCO3 solution (100 mL) was added
  3. extractionthe product extracted with 2-MeTHF (4×100 mL)
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified
  8. washeluting with 0-40% acetonitrile in water
  9. dissolutionThe resulting solid was dissolved in MeCN (40 mL) at 50° C.
  10. additionmethanol added
  11. temperatureto cool
  12. customThe resulting white precipitate was collected
  13. customdried
  14. customfurther triturated with EtOAc (5 mL) twice
  15. customto afford a white solid as the

Sources & evidence

ORD record
ord-f8e4410515824993a3c0708f9d70f99c
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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