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

反応式

HRID 84661 の反応式
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

参加物

11

反応物 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

生成物 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 amide収率 21%

試薬・触媒・溶媒 5

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

反応条件

温度
150 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-975510443fa6406eb9d16d7e7ccdce26
出典データセット
uspto-grants-2014_09
特許番号
US08846762B2

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