Benzophenone imine → HCID 86647077, compound

HRID 1812350Notes

Reaction equation

HRID 1812350 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:9]([S:14]([CH3:17])(=[O:16])=[O:15])S(C)(=O)=O)[C:5]([Cl:8])=[N:6][CH:7]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC([O-])(C)C.[Na+].[C:66]1([C:72]([C:74]2[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=2)=[NH:73])[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:8][C:5]1[C:4]([NH:9][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:3][C:2]([N:73]=[C:72]([C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)[C:74]2[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=2)=[CH:7][N:6]=1

Participants

7

Reactant 4

HCID 136809Benzophenone imineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 46941444HCID 46941444, compound

Product 1

HCID 86647077HCID 86647077, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a 20 mL microwave reaction tube was added N-(5-bromo-2-chloropyridin-3-yl)-N-(methylsulfonyl)methanesulfonamide (Step 0) 1.11 g, 3.04 mmol), xantphos (0.179 g, 0.308 mmol), NaOtBu (1.18 g, 12.3 mmol), Pd2dba3 (0.139 g, 0.152 mmol) and diphenylmethanimine (0.62 mL, 3.7 mmol) in DMF (10 mL). The mixture was degassed by bubbling argon through for 10 min. The tube was heated in Initiator microwave reactor (Biotage) at 120° C. for 30 min. The reaction mixture was partitioned between tris-HCl buffer (1 M, pH 7.0) (80 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (2×60 mL). The combined organic phases were washed with water (200 mL) and saturated aqueous sodium chloride (150 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (100 g, eluent: EtOAc in hexanes 0% to 50%) to afford N-(2-chloro-5-(diphenylmethyleneamino)pyridin-3-yl)methanesulfonamide (0.90 g, 77% yield) as a light brown solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.72-7.77 (m, 3H) 7.50-7.56 (m, 1H) 7.43 (t, J=7.53 Hz, 2H) 7.32-7.37 (m, 3H) 7.28-7.31 (m, 1H) 7.11-7.16 (m, 2H) 6.66 (s, 1H) 2.78 (s, 3H).

Workup

  1. customThe mixture was degassed
  2. customby bubbling argon through for 10 min
  3. customThe reaction mixture was partitioned between tris-HCl buffer (1 M, pH 7.0) (80 mL) and EtOAc (50 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (2×60 mL)
  5. washThe combined organic phases were washed with water (200 mL) and saturated aqueous sodium chloride (150 mL)
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by silica gel column chromatography (100 g, eluent: EtOAc in hexanes 0% to 50%)

Sources & evidence

ORD record
ord-a243cf3f69b34e7d853f362326915b49
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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