Triethylamine → (E)-2-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-ethenesulfonic acid amide

HRID 886454Notes

Reaction equation

HRID 886454 reaction equation
Br[C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:18]([CH:19]([CH3:21])[CH3:20])[N:17]=[CH:16][N:15]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.[CH:24]([S:26]([NH2:29])(=[O:28])=[O:27])=[CH2:25].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:19]([N:18]1[C:14]([C:12]2[N:13]=[C:6]3[N:7]([CH2:8][CH2:9][O:10][C:4]4[CH:3]=[C:2](/[CH:25]=[CH:24]/[S:26]([NH2:29])(=[O:28])=[O:27])[CH:23]=[CH:22][C:5]=43)[CH:11]=2)=[N:15][CH:16]=[N:17]1)([CH3:21])[CH3:20]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 520075Vinyl sulfonamideHCID 582043138-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

Product 1

HCID 58204452(E)-2-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-ethenesulfonic acid amideYield 35.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

8-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene 194 (400 mg, 1.07 mmol), ethenesulfonic acid amide (172 mg, 1.60 mmol), triethylamine (223 μL, 1.60 mmol), tri-o-tolyl-phosphane (65 mg, 0.21 mmol) and palladium (II) acetate (12 mg, 0.05 mmol) were suspended in DMF (5 mL) and the reaction mixture degassed by bubbling argon through the suspension. The reaction mixture was heated at 130° C. for 16 h, before cooling to RT and diluting the mixture with ethyl acetate (10 mL). The resultant mixture was washed with water, extracted with ethyl acetate (2×10 mL) and the combined organic extracts washed with brine, dried (MgSO4) then concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-10% methanol in DCM) to yield the title compound as a white solid (151 mg, 35%) LCMS: RT=2.69 min, [M+H]+=401.

Workup

  1. customthe reaction mixture degassed
  2. customby bubbling argon through the suspension
  3. temperaturebefore cooling to RT
  4. additiondiluting the mixture with ethyl acetate (10 mL)
  5. washThe resultant mixture was washed with water
  6. extractionextracted with ethyl acetate (2×10 mL)
  7. washthe combined organic extracts washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationthen concentrated in vacuo
  10. washThe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-10% methanol in DCM)

Sources & evidence

ORD record
ord-d4c74a1b456145bb941a62337ef3b9d7
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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