Acetonitrile → HCID 46869255, compound

HRID 578666Notes

Reaction equation

HRID 578666 reaction equation
[CH2:1]([N:3](S(C1C=CC([N+]([O-])=O)=CC=1)(=O)=O)[CH2:4][C@@H:5]([NH:12][C:13]1[C:22]2[C:17](=[C:18]([C:23]([NH2:25])=[O:24])[CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][N:14]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH3:2].C(#N)C.C(=O)([O-])[O-].[Cs+].[Cs+].C1(S)C=CC=CC=1>[NH4+].[Cl-]>[CH2:1]([NH:3][CH2:4][C@@H:5]([NH:12][C:13]1[C:22]2[C:17](=[C:18]([C:23]([NH2:25])=[O:24])[CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][N:14]=1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)[CH3:2]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 7969ThiophenolHCID 10796Cesium carbonateHCID 66763582HCID 66763582, compound

Product 1

HCID 46869255HCID 46869255, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Procedure

To a 40-mL vial with magnetic stirbar at 25° C. under a nitrogen atmosphere was added 4-{(S)-2-[Ethyl-(4-nitro-benzenesulfonyl)-amino]-1-phenyl-ethylamino}-quinazoline-8-carboxylic acid amide (0.45 g, 0.86 mmol, 1 eq.) and anhydrous acetonitrile (25 mL). The Cesium carbonate (0.84 g, 2.6 mmol, 3 eq.) was added followed by the thiophenol (0.14 g, 1.3 mmol, 0.13 mL, 1.5 eq.). Stirring was continued at 25° C.×16 hours. The reaction mixture was diluted with saturated aqueous NH4Cl solution (40 mL) and extracted with EtOAc (30 mL)×3. The combined organics were washed with brine (20 mL), dried (e.g., Na2SO4), filtered and concentrated. The resulting residue was purified by column chromatography (ISCO CombiFlash) using a 0-100% gradient (10% MeOH in EtOAc/EtOAc) to afford 58.3 mg (21% yield). LCMS (ESI) 336.2 (M+H).

Workup

  1. customwas continued at 25° C.
  2. custom×16 hours
  3. extractionextracted with EtOAc (30 mL)×3
  4. washThe combined organics were washed with brine (20 mL)
  5. dry with materialdried (e.g., Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by column chromatography (ISCO CombiFlash)
  9. customto afford 58.3 mg (21% yield)

Sources & evidence

ORD record
ord-31ab1d48f97a4fd5aff59e91ae7998c8
Source dataset
uspto-grants-2015_05
Patent number
US09040560B2

Reaction notes

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