Benzophenone imine → N-(2-chloro-5-(diphenylmethyleneamino)pyridin-3-yl)morpholine-4-sulfonamide

HRID 1622008Notes

Reaction equation

HRID 1622008 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:9][S:10]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].[C:67](=[NH:80])([C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1)[C:68]1[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Cl:8][C:5]1[C:4]([NH:9][S:10]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)(=[O:12])=[O:11])=[CH:3][C:2]([N:80]=[C:67]([C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=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 59519519HCID 59519519, compound

Product 1

HCID 86647078N-(2-chloro-5-(diphenylmethyleneamino)pyridin-3-yl)morpholine-4-sulfonamideYield 23.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a 20 mL microwave vial was added N-(5-bromo-2-chloropyridin-3-yl)morpholine-4-sulfonamide (0.500 g, 1.40 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Acros) (0.048 g, 0.084 mmol), tris(dibenzylideneacetone)dipalladium (o) (Strem) (0.015 g, 0.017 mmol), sodium tert-butoxide (Fluka) (0.268 g, 2.8 mmol), toluene (10 mL), and benzophenone imine (Aldrich) (0.260 mL, 1.54 mmol). The resulting mixture was sealed off and microwave heated at 110° C. for 20 min. Reaction mixture was partitioned between EtOAc and Tris HCl 1M pH7. The aqueous layer was extracted with EtOAc (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (24 g, 10% to 20% EtOAc in hexanes) to afford the desired product as a yellow foam (150.0 mg). MS (ESI pos. ion) m/z: 457.0. 1H NMR (300 MHz, CDCl3) δ ppm 3.07 (d, J=4.38 Hz, 4H) 3.63 (d, J=4.38 Hz, 4H) 6.62 (br. s., 1H) 7.14 (d, J=3.95 Hz, 2H) 7.35 (d, J=5.85 Hz, 4H) 7.40-7.49 (m, 2H) 7.49-7.58 (m, 1H) 7.63 (s, 1H) 7.74 (d, J=7.16 Hz, 2H).

Workup

  1. customThe resulting mixture was sealed off
  2. customReaction mixture
  3. customwas partitioned between EtOAc and Tris HCl 1M pH7
  4. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (24 g, 10% to 20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-acb840fd4a314984a3244ec202b6b698
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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