Cesium carbonate → [7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[4-(piperazine-1-sulfonyl)-phenyl]-amine HCl salt

HRID 449229Notes

Reaction equation

HRID 449229 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[CH:19]=[C:18]([CH3:20])[C:12]2[N:13]=[C:14]([NH2:17])[N:15]=[N:16][C:11]=2[CH:10]=1.Br[C:22]1[CH:27]=[CH:26][C:25]([S:28]([N:31]([CH:39]([CH3:41])C)[CH2:32][CH2:33][N:34]2CCCC2)(=[O:30])=[O:29])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[CH:19]=[C:18]([CH3:20])[C:12]2[N:13]=[C:14]([NH:17][C:22]3[CH:23]=[CH:24][C:25]([S:28]([N:31]4[CH2:32][CH2:33][NH:34][CH2:41][CH2:39]4)(=[O:29])=[O:30])=[CH:26][CH:27]=3)[N:15]=[N:16][C:11]=2[CH:10]=1

Participants

6

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 598377604-bromo-N-isopropyl-N-(2-pyrrolidin-1-yl-ethyl)-benzenesulfonamide

Product 1

HCID 68982670[7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[4-(piperazine-1-sulfonyl)-phenyl]-amine HCl salt

Reagents, catalysts & solvents 1

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalyst

Procedure

In a dry 25 mL round bottom flask, 7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine (0.162 g, 0.533 mmol, 1 equiv), 4-bromo-N-isopropyl-N-(2-pyrrolidin-1-yl-ethyl)-benzenesulfonamide (0.3 g, 0.8 mmol, 1.5 equiv), cesium carbonate (0.522 g, 1.59 mmol, 3 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethyl xanthene (0.062 g, 0.106 mmol, 0.2 equiv) and tris(dibenzylideneacetone) dipalladium (0.049 g, 0.0533 mmol, 0.1 equiv) were combined. The reactants were flushed with argon, diluted with dioxane (20 mL), and outfitted with a reflux condenser. The reaction was heated to reflux for 2 hours, then filtered hot and the solvents were evaporated. Purification on silica gel flash column provided desired product, 0.144 g yellow solids, which were taken up in 5 mL DCM and treated with 2 mL 2M HCl in ether solution. The solvents were then evaporated and the resulting solids were collected and dried to yield a yellow solid (0.16 g, 50% yield). MS (ESI+): m/z=599.2, LC retention time: 2.99 min. 1H NMR (DMSO-d6): δ 0.98 (d, 6H), 1.88 (m, 2 H), 2.01 (m, 2H), 2.72 (s, 3H), 3.02-108 (m, 2H), 3.37 (m, 2H), 3.46 (m, 2H), 3.62 (m, 2H), 4.02 (m, 1H), 7.53 (m, 1H), 7.67 (d, J=8.1 Hz, 2H), 7.79 (s, 1H), 7.92 (d, J=8.7 Hz, 2H), 8.18 (d, J=1.6 Hz, 1H), 8.27 (d, J=8.7 Hz, 2H), 10.7 (m, 1H), 11.51 (s, 1H).

Workup

  1. customThe reactants were flushed with argon
  2. additiondiluted with dioxane (20 mL)
  3. customoutfitted with a reflux condenser
  4. temperatureThe reaction was heated
  5. temperatureto reflux for 2 hours
  6. filtrationfiltered hot
  7. customthe solvents were evaporated
  8. customPurification on silica gel flash column

Sources & evidence

ORD record
ord-d640feae33ca44e596fc43acc3cef581
Source dataset
uspto-grants-2013_07
Patent number
US08481536B2

Reaction notes

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