Cesium carbonate → 4-[7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-N-methyl-N-(2-pyrrolidin-1-yl-ethyl)-benzenesulfonamide

HRID 273512Notes

Reaction equation

HRID 273512 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH3:19])[CH2:12][CH2:13][N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=1[C:28]1[CH:38]=[C:37]([CH3:39])[C:31]2[N:32]=[C:33]([NH2:36])[N:34]=[N:35][C:30]=2[CH:29]=1.C([O-])([O-])=O.[Cs+].[Cs+].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>O1CCOCC1.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:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=1[C:28]1[CH:38]=[C:37]([CH3:39])[C:31]2[N:32]=[C:33]([NH:36][C:2]3[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH3:19])[CH2:12][CH2:13][N:14]4[CH2:18][CH2:17][CH2:16][CH2:15]4)(=[O:10])=[O:9])=[CH:4][CH:3]=3)[N:34]=[N:35][C:30]=2[CH:29]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 248227577-(2,6-Dichlorophenyl)-5-methylbenzo[e][1,2,4]triazin-3-amineHCID 598376194-bromo-N-methyl-N-(2-pyrrolidin-1-yl-ethyl)-benzenesulfonamide

Product 1

HCID 598376204-[7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-N-methyl-N-(2-pyrrolidin-1-yl-ethyl)-benzenesulfonamideYield 76%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-bromo-N-methyl-N-(2-pyrrolidin-1-yl-ethyl)-benzenesulfonamide (1.0 equiv, 0.82 mmol), 7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine (1.5 equiv, 1.23 mmol), Cs2CO3 (3.0 equiv, 2.46 mmol), Pd2(dba)3 (0.1 equiv, 0.082 mmol), and Xantphos (0.2 equiv, 0.1634 mmol) were dissolved in 15 mL dioxane and purged of air, then placed under an argon blanket and refluxed for 18 h at 100° C. The reaction was cooled to room temperature and filtered and condensed under reduced pressure. The residue that was recovered was dissolved in EtOAc and extracted with saturated bicarbonate and brine; the organics were then dried (Na2SO4) and concentrated to afford brown oil. Using EtOAc/hexanes (1:5 v/v) the residue was precipitated out to afford 4-[7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-N-methyl-N-(2-pyrrolidin-1-yl-ethyl)-benzenesulfonamide, as a tan solid, (297.2 mg, 76% yield). 1H NMR (DMSO-d6): δ 1.95 (dm, 4H), 2.72 (s, 3H), 2.73 (s, 3H), 3.04 (q, J=7.5 Hz, 2H), 3.35 (dt, J=5.3 Hz, J=5.4 Hz, 4H), 3.58 (q, J=5.2 Hz, 2H), 7.52 (t, J=7.6 Hz, 1H), 7.67 (d, J=3.2 Hz, 2H), 7.79 (s, 1H), 7.87 (d, J=3.2 Hz, 2H), 8.18 (s, 1H), 8.31 (s, J=9.0 Hz, 2H), 10.51 (bs, 1H), 11.55 (s, 1H). MS (ES+) m/z=574, LC retention time 2.80 minutes.

Workup

  1. custompurged of air
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered
  4. customcondensed under reduced pressure
  5. customThe residue that was recovered
  6. dissolutionwas dissolved in EtOAc
  7. extractionextracted with saturated bicarbonate and brine
  8. dry with materialthe organics were then dried (Na2SO4)
  9. concentrationconcentrated
  10. customto afford brown oil
  11. customUsing EtOAc/hexanes (1:5 v/v) the residue was precipitated out

Sources & evidence

ORD record
ord-d0fffceb8b374584b9df5ceb9970d483
Source dataset
uspto-grants-2008_11
Patent number
US07456176B2

Reaction notes

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