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 84661

반응식

HRID 84661 반응식
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

참가 물질

11

반응물 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

생성물 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 amide수율 21%

시약·촉매·용매 5

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

반응 조건

온도
150 °C

실험 절차

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 (1 H, d, J=8.3 Hz), 7.99 (1H, bs), 7.72 (1 H, d, J=0.7 Hz), 7.66 (1 H, dd, J=8.3, 1.8 Hz), 7.57 (1 H, d, J=1.8 Hz), 7.40 (1 H, bs), 4.41 (2 H, t, J=5.0 Hz), 3.45 (2 H, t, J=5.0 Hz), 2.74-2.66 (1 H, m), 1.23-1.15 (2 H, m), 0.93-0.87 (2 H, m).

후처리

  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

출처 및 근거

ORD 기록
ord-975510443fa6406eb9d16d7e7ccdce26
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846762B2

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