Cesium carbonate → [7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[3-(4-methyl-piperazine-1-sulfonyl)-phenyl]-amine

HRID 449202Notes

Reaction equation

HRID 449202 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:20]=[C:19]([CH3:21])[C:13]2[N:14]=[C:15]([NH2:18])[N:16]=[N:17][C:12]=2[CH:11]=1.Br[C:23]1[CH:24]=[C:25]([S:29]([N:32]2[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]2)(=[O:31])=[O:30])[CH:26]=[CH:27][CH:28]=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:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:20]=[C:19]([CH3:21])[C:13]2[N:14]=[C:15]([NH:18][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([S:29]([N:32]4[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]4)(=[O:31])=[O:30])[CH:24]=3)[N:16]=[N:17][C:12]=2[CH:11]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 248227537-(2-Chloro-5-methoxyphenyl)-5-methylbenzo[e][1,2,4]triazin-3-amineHCID 294021141-(3-Bromobenzenesulfonyl)-4-methylpiperazine

Product 1

HCID 59837628[7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[3-(4-methyl-piperazine-1-sulfonyl)-phenyl]-amine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine (0.315 mmol, 1.0 equiv), 1-(3-bromo-benzenesulfonyl)-4-methyl-piperazine (0.472 mmol, 1.5 equiv), Pd2(dba)3 (0.0315 mmol, 0.1 equiv), Cs2CO3 (0.945 mmol, 3.0 equiv), and Xantphos (0.063 mmol, 0.2 equiv) were dissolved in 10 mL of dioxane, purged of air and placed under an argon atmosphere to reflux at 100° C. for 18 h. The reaction was cooled to room temperature and filtered to remove excess Cs2CO3. The filtrate was extracted with EtOAc and washed with saturated NaHCO3 and brine, and the organics were dried (Na2SO4). The organics were removed under reduced pressure to afford brown residue which was precipitated using DCM/Et2O (1:5 v/v) to give [7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[3-(4-methyl-piperazine-1-sulfonyl)-phenyl]-amine, as a yellow solid (45 mg, 27% yield). 1H NMR (DMSO-d6): δ 2.12 (s, 3H), 2.37 (m, 4H), 2.71 (s, 3H), 2.95 (m, 4H), 3.83 (s, 3H), 7.06 (dd, J=8.9 Hz, J=3.1 Hz, 1H), 7.14 (d, J=3.1 Hz, 1H), 7.41 (dd, J=6.3 Hz, J=1.1 Hz, 1H), 7.54 (d, J=8.7 Hz, 1H), 7.67 (t, J=8.1 Hz, 2H), 8.06 (dd, J=7.6 Hz, J=1.6 Hz, 1H), 8.27 (d, J=1.9 Hz, 1H), 8.9 (bs, 1H). MS (ES+): m/z=540 LC retention time 2.70 min.

Workup

  1. custompurged of air
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered
  4. customto remove excess Cs2CO3
  5. extractionThe filtrate was extracted with EtOAc
  6. washwashed with saturated NaHCO3 and brine
  7. dry with materialthe organics were dried (Na2SO4)
  8. customThe organics were removed under reduced pressure
  9. customto afford brown residue which
  10. customwas precipitated

Sources & evidence

ORD record
ord-95f4e630f853493ebe20609b5ae2ae87
Source dataset
uspto-grants-2013_07
Patent number
US08481536B2

Reaction notes

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