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

HRID 1812359Notes

Reaction equation

HRID 1812359 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.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:67]1([C:73]([C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=2)=[NH:74])[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=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:10]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)(=[O:12])=[O:11])=[CH:3][C:2]([N:74]=[C:73]([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)[C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=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 72%

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)morpholine-4-sulfonamide (Example 366, Step 3) 0.510 g, 1.43 mmol), xantphos (0.0839 g, 0.145 mmol), Pd2dba3 (0.0646 g, 0.071 mmol), NaOtBu (Aldrich, 0.418 g, 4.35 mmol) and diphenylmethanimine (Aldrich, 0.264 mL, 1.57 mmol) in DMF (6 mL). The mixture was degassed by bubbling argon through for 5 min. The tube was heated in a microwave reactor (Biotage) at 120° C. for 30 min. The reaction mixture was partitioned between saturated aqueous ammonium chloride (40 mL) and EtOAc (40 mL). The aqueous phase was extracted with EtOAc (2×40 mL). The combined organic phases were washed with water (80 mL) and saturated aqueous sodium chloride (80 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 70%) to afford N-(2-chloro-5-(diphenylmethyleneamino)pyridin-3-yl)morpholine-4-sulfonamide in 2 fractions (total 0.42 g, 72% yield) as a yellow solid (0.26 g) and a light brown solid (0.21 g). 1H NMR (400 MHz, CDCl3) δ ppm 7.73 (d, J=7.43 Hz, 2H) 7.62 (d, J=2.35 Hz, 1H) 7.49-7.55 (m, 1H) 7.43 (t, J=7.53 Hz, 2H) 7.31-7.37 (m, 4H) 7.11-7.16 (m, 2H) 6.63 (br. s., 1H) 3.60-3.65 (m, 4H) 3.03-3.09 (m, 4H).

Workup

  1. customThe mixture was degassed
  2. customby bubbling argon through for 5 min
  3. customThe reaction mixture was partitioned between saturated aqueous ammonium chloride (40 mL) and EtOAc (40 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (2×40 mL)
  5. washThe combined organic phases were washed with water (80 mL) and saturated aqueous sodium chloride (80 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 70%)

Sources & evidence

ORD record
ord-f4fab450c4b24f64840d6dbb2f304089
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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