5-Ethylsulphonyl-o-anisidine → HCID 86608154, compound

HRID 2374961Notes

Reaction equation

HRID 2374961 reaction equation
BrC1C=C([C:8]2[N:16]3[C:11]([CH:12]=[N:13][C:14]([NH:17][C:18]4[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[C:20]([O:28][CH3:29])[CH:19]=4)=[N:15]3)=[C:10]([CH3:30])[N:9]=2)C=CC=1.C(S(C1C=CC(OC)=C(C=1)N)(=O)=O)C.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>O1CCOCC1>[CH3:30][C:10]1[N:9]=[CH:8][N:16]2[C:11]=1[CH:12]=[N:13][C:14]([NH:17][C:18]1[CH:19]=[C:20]([O:28][CH3:29])[C:21]([O:26][CH3:27])=[C:22]([O:24][CH3:25])[CH:23]=1)=[N:15]2

Participants

6

Reactant 4

HCID 792785-Ethylsulphonyl-o-anisidineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 112135557-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)-imidazo[5,1-f][1,2,4]triazin-2-amineHCID 23676156Sodium t-butoxide

Product 1

HCID 86608154HCID 86608154, compoundYield 59.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

To a mixture of 7-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (Example 9) (49.1 mg, 0.104 mmol), 5-(ethylsulfonyl)-2-methoxyaniline (22.5 mg, 0.104 mmol), 2-(dit-butylphosphino)biphenyl (16.3 mg, 0.054 mmol), Tris(dibenzylidineacetone)dipalladium (0) (16.6 mg, 0.018 mmol) and sodium t-butoxide (26.0 mg, 0.28 mmol) was added 1,4-dioxane (1.0 mL). In a sealed reaction vessel, the mixture was heated with microwave radiation at 130° C. for 50 minutes. After cooling to room temperature, removed solvent under reduced pressure and diluted residue in dichloromethane. Filtered and added silica gel (500 mg) to filtrate followed by evaporation of the volatiles under reduced pressure. The pre-adsorbed solids were loaded into a solid loading cartridge and subjected to a gradient elution using ethyl acetate:hexanes (25:75) to ethyl acetate:hexanes (95:5) using a RediSep silica gel cartridge (4.2 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give 7-(3-{[5-ethylsulfonyl)-2-methoxyphenyl]amino}phenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)imidazo-[5,1-f][1,2,4]triazin-2-amine (0.0195 g) as a yellow solid. 1H NMR (CDCl3): δ8.82 (s, 1H), 8.39 (s, 1H), 8.17 (d, J=7.7 Hz, 1H), 7.82 (s, 1H), 7.42-7.19 (m, 4H), 6.97 (d, J=7.3 Hz, 1H), 6.88 (s, 2H), 6.45 (s, 1H) 4.00 (s, 3H) 3.84 (s, 9H), 3.06 (d, J=6.6 Hz, 2H), 2.60 (s, 3H), 1.25 (m, 3H). MS m/z 605 (M+1).

Workup

  1. customIn a sealed reaction vessel
  2. temperatureAfter cooling to room temperature
  3. customremoved solvent under reduced pressure and diluted residue in dichloromethane
  4. filtrationFiltered
  5. additionadded silica gel (500 mg) to filtrate
  6. customfollowed by evaporation of the volatiles under reduced pressure
  7. washsubjected to a gradient elution
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-57fe47980adb4a5487f74a4e155bd88e
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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