1,8-Diazabicyclo(5.4.0)undec-7-ene → 2-(5-Cyclopropyl-[1,2,3]triazol-1-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-8-carboxylic acid amide

HRID 2079030Notes

Reaction equation

HRID 2079030 reaction equation
Br[C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:7]=[C:8]([N:14]4[C:18]([CH:19]5[CH2:21][CH2:20]5)=[CH:17][N:16]=[N:15]4)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1.Cl.N[OH:26].F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[N:45]12[CH2:55]CCN=C1CCCCC2.CCN(C(C)C)C(C)C>O1CCOCC1.C(OCC)(=O)C.CS(C)=O.O.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd]>[CH:19]1([C:18]2[N:14]([C:8]3[S:9][C:10]4[CH2:11][CH2:12][O:13][C:4]5[CH:3]=[C:2]([C:55]([NH2:45])=[O:26])[CH:23]=[CH:22][C:5]=5[C:6]=4[N:7]=3)[N:15]=[N:16][CH:17]=2)[CH2:21][CH2:20]1

Participants

11

Reactant 5

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81531DiisopropylethylamineHCID 443297Hydroxyamine hydrochlorideHCID 44558591Tri-t-butylphosphine fluoroborateHCID 579002148-Bromo-2-(5-cyclopropyl-[1,2,3]triazol-1-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

Product 1

HCID 532348972-(5-Cyclopropyl-[1,2,3]triazol-1-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-8-carboxylic acid amideYield 21%

Reagents, catalysts & solvents 5

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 23503278(Methanesulfinyl)methane--water (1/1)Solvent

Conditions

Temperature
150 °C

Procedure

To a suspension of 8-bromo-2-(5-cyclopropyl-[1,2,3]triazol-1-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (224 mg, 0.58 mmol), hydroxylamine hydrochloride (81 mg, 1.16 mmol), molybdenum hexacarbonyl (77 mg, 0.29 mmol), tri-tert-butylphosphine tetrafluoroborate (17 mg, 0.058 mmol), trans-di-μ-acetatobis[2-(di-o-tolylphosphino)benzyl]dipalladium(II) (27 mg, 0.029 mmol) in dioxane (7 mL) were added 1,8-diazabicyclo[5.4.0]undec-7-ene (86 μL, 0.58 mmol) and DIPEA (197 μL, 1.16 mmol). The reaction mixture was heated at 150° C. under microwave irradiation for 30 mins, and diluted with ethyl acetate. The organic layer was washed successively with water, aqueous saturated ammonium chloride, aqueous saturated sodium bicarbonate solution and brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, 3% MeOH in DCM) to give an off-white solid, which was dissolved in DMSO/water. The mixture was left to stand at RT for 7 days, filtered, and the filtrate was diluted with ethyl acetate and water. The organic layer was washed with brine, dried (Na2SO4) and concentrated in vacuo to give 414 as an off-white solid (42 mg, 21%). LCMS (Method C): RT=8.65 min, [M+H]+=354. 1H NMR (DMSO-d6): 8.32 (1H, d, J=8.3 Hz), 7.99 (1H, bs), 7.72 (1H, d, J=0.7 Hz), 7.66 (1H, dd, J=8.3, 1.8 Hz), 7.57 (1H, d, J=1.8 Hz), 7.40 (1H, bs), 4.41 (2H, t, J=5.0 Hz), 3.45 (2H, t, J=5.0 Hz), 2.74-2.66 (1H, m), 1.23-1.15 (2H, m), 0.93-0.87 (2H, m).

Workup

  1. washThe organic layer was washed successively with water, aqueous saturated ammonium chloride, aqueous saturated sodium bicarbonate solution and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resultant residue was purified by flash chromatography (SiO2, 3% MeOH in DCM)
  5. customto give an off-white solid, which
  6. waitThe mixture was left
  7. filtrationfiltered
  8. additionthe filtrate was diluted with ethyl acetate and water
  9. washThe organic layer was washed with brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e8ba62b1135e49e8bdd2f63d8b91765f
Source dataset
uspto-grants-2011_04
Patent number
US07928248B2

Reaction notes

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