Cesium carbonate → 5-(2-phenylpyrrolidin-1-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

HRID 1473345Notes

Reaction equation

HRID 1473345 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([S:12]([N:15](CC1C=CC(OC)=CC=1OC)[C:16]1[S:20][N:19]=[CH:18][N:17]=1)(=[O:14])=[O:13])=[CH:7]2.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.C(=O)([O-])[O-].[Cs+].[Cs+].[C:80]1([CH:86]2[CH2:90][CH2:89][CH2:88][NH:87]2)[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=1>C(Cl)Cl.C(O)(C(F)(F)F)=O.CO.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>[C:80]1([CH:86]2[CH2:90][CH2:89][CH2:88][N:87]2[C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][C:6]([S:12]([NH:15][C:16]2[S:20][N:19]=[CH:18][N:17]=2)(=[O:14])=[O:13])=[CH:7]3)[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=1

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 2618922-PhenylpyrrolidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866873455-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

Product 1

HCID 866873955-(2-phenylpyrrolidin-1-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamideYield 44.7%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with 5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (205 mg, 0.394 mmol), Xantphos (45.6 mg, 0.079 mmol), Pd2(dba)3 (36.1 mg, 0.039 mmol), and cesium carbonate (257 mg, 0.788 mmol). The vial was flushed with Ar (g), then toluene (3939 μl) and 2-phenylpyrrolidine (81 μl, 0.551 mmol) were added in sequence. The vial was sealed and heated at 100° C. for 16 h. The reaction mixture was partitioned between EtOAc and water. The layers were separated, and the organic extract was washed with brine. The combined aq. layers were extracted with EtOAc, and the organic layers were combined. The combined solution was washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel with 0 to 50% EtOAc/Heptane to give a clear oil. This material was dissolved in DCM (2 mL) and TFA (1 mL), and the resulting mixture was stirred for 2 h. The mixture was diluted with MeOH, then concentrated. The crude product was purified by chromatography on silica gel with 0 to 5% MeOH/DCM to give 5-(2-phenylpyrrolidin-1-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (76.7 mg, 0.176 mmol) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.55-8.46 (m, 2H), 8.34 (d, J=2.1 Hz, 1H), 7.78 (dd, J=2.1, 9.0 Hz, 1H), 7.63 (d, J=8.2 Hz, 1H), 7.43-7.33 (m, 3H), 7.22-7.16 (m, 2H), 7.12-7.06 (m, 2H), 4.82 (dd, J=6.3, 9.1 Hz, 1H), 4.19-4.12 (m, 1H), 3.03 (dt, J=4.5, 8.9 Hz, 1H), 2.47-2.40 (m, 1H), 2.14-2.10 (m, 1H), 2.00-1.79 (m, 2H). m/z (ESI) 437.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. customThe vial was sealed
  3. customThe reaction mixture was partitioned between EtOAc and water
  4. customThe layers were separated
  5. extractionthe organic extract
  6. washwas washed with brine
  7. extractionThe combined aq. layers were extracted with EtOAc
  8. washThe combined solution was washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by chromatography on silica gel with 0 to 50% EtOAc/Heptane
  13. customto give a clear oil
  14. concentrationconcentrated
  15. customThe crude product was purified by chromatography on silica gel with 0 to 5% MeOH/DCM

Sources & evidence

ORD record
ord-308c97f689c943b9871bb235b329b4c0
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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