Acetonitrile → HCID 46869255, compound

HRID 474430Notes

Reaction equation

HRID 474430 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-8978c0b87d0e48499181a4a6d80c07a6
Source dataset
uspto-grants-2014_01
Patent number
US08637532B2

Reaction notes

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