Methyl Methacrylate → HCID 67050705, compound

HRID 1800268Notes

Reaction equation

HRID 1800268 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.[C:24]([O:29][CH3:30])(=[O:28])[C:25]([CH3:27])=[CH2:26].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>[CH3:30][O:29][C:24](=[O:28])/[C:25](/[CH3:27])=[CH:26]/[C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:7]([CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1)[CH:11]=[C:12]([C:14]1[N:18]([CH:19]([CH3:21])[CH3:20])[N:17]=[CH:16][N:15]=1)[N:13]=3

Participants

7

Reactant 4

HCID 6658Methyl MethacrylateHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 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 67050705HCID 67050705, compoundYield 57.5%

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 (300 mg, 0.80 mmol), methyl methacrylate (129 μL, 1.20 mmol), triethylamine (168 μL, 1.20 mmol), tri-o-tolyl-phosphane (49 mg, 0.16 mmol) and palladium (II) acetate (9 mg, 0.04 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 reaction 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 0-5% methanol in DCM) to yield (E)-3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-2-methyl-acrylic acid methyl ester as a white solid (181 mg, 57%) LCMS: RT=3.63 min, [M+H]+=394.

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 reaction 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 0-5% methanol in DCM)

Sources & evidence

ORD record
ord-dd71dcb0b2564e08b6d929933e3b48e2
Source dataset
uspto-grants-2013_01
Patent number
US08343955B2

Reaction notes

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