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

HRID 273533

Reaktionsgleichung

Reaktionsgleichung von HRID 273533
[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]([NH:31][CH2:32][CH2:33][N:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)(=[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>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]>[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:27]=[CH:26][C:25]([S:28]([NH:31][CH2:32][CH2:33][N:34]4[CH2:35][CH2:36][CH2:37][CH2:38]4)(=[O:30])=[O:29])=[CH:24][CH:23]=3)[N:15]=[N:16][C:11]=2[CH:10]=1

Komponenten

6

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 40330904-Bromo-N-(2-(pyrrolidin-1-yl)ethyl)benzenesulfonamideHCID 248227577-(2,6-Dichlorophenyl)-5-methylbenzo[e][1,2,4]triazin-3-amine

Produkt 1

HCID 689810514-[7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-N-(2-pyrrolidin-1-yl-ethyl)-benzenesulfonamide HCl salt

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Versuchsvorschrift

In a dry 25 mL round bottom flask, 7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine (0.193 g, 0.633 mmol, 1 equiv), 4-bromo-N-(2-pyrrolidin-1-yl-ethyl)-benzenesulfonamide (0.316 g, 0.95 mmol, 1.5 equiv), cesium carbonate (0.62 g, 1.89 mmol, 3 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethyl xanthene (0.073 g, 0.127 mmol, 0.2 equiv) and tris(dibenzylideneacetone)dipalladium (0.058 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 16 hours, then filtered hot and the solvents were evaporated. HPLC purification provided desired product. Pure HPLC fractions were combined, diluted with ethyl acetate and washed with saturated sodium bicarbonate solution. The organic phase was evaporated to dryness, diluted with DCM (10 mL) 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 (0.091 g, 26% yield). MS (ESI+): m/z=559.6, LC retention time: 2.71 min. 1H NMR (DMSO-d6): δ 1.86 (bs, 2H), 1.98 (bs, 2H), 2.71 (s, 3H), 2.98-3.01 (m, 2H), 3.09-3.13 (m, 2H), 3.21-3.25 (m, 2H), 3.51-3.53 (m, 2H), 7.52 (m, 1H), 7.67 (d, J=8.7 Hz, 2H), 7.79 (m, 1H), 7.89 (dd, J=8.7 Hz, J=2.9 Hz, 1H), 7.95 (t, J=6.1 Hz, 1H), 8.18 (d, J=1.7 Hz, 1H), 8.26 (d, J=8.8 Hz, 2H), 10.37 (bs, 1H), 11.44 (s, 1H).

Aufarbeitung

  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 16 hours
  6. filtrationfiltered hot
  7. customthe solvents were evaporated
  8. customHPLC purification

Quellen und Nachweise

ORD-Eintrag
ord-ad70ad5c04874953bbdaa255036e668b
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07456176B2

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