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Cesium carbonate → 7-(2-Fluorophenyl)-4-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-(thien-3-yl)pyrazolo[1,5-d][1,2,4]triazine

HRID 985443
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HRID 985443 반응식
Br[C:2]1[C:3]([O:19][CH2:20][C:21]2[N:22]([CH3:26])[N:23]=[CH:24][N:25]=2)=[N:4][N:5]2[C:10]=1[C:9]([CH3:11])=[N:8][N:7]=[C:6]2[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18].[S:27]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:6]1[N:5]2[N:4]=[C:3]([O:19][CH2:20][C:21]3[N:22]([CH3:26])[N:23]=[CH:24][N:25]=3)[C:2]([C:29]3[CH:30]=[CH:31][S:27][CH:28]=3)=[C:10]2[C:9]([CH3:11])=[N:8][N:7]=1
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7

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HCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 581760Thiophene-3-boronic acidHCID 225068923-bromo-7-(2-fluorophenyl)-4-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine

생성물 1

HCID 101804997-(2-Fluorophenyl)-4-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-(thien-3-yl)pyrazolo[1,5-d][1,2,4]triazine
수율 83%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매2회

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온도
90 °C

실험 절차

A mixture of 3-bromo-7-(2-fluorophenyl)-4-methyl-2-(2-methyl-2H-[1,2,4]triazol-3ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (100.7 mg, 0.241 mmol), thiophene-3-boronic acid (46.8 mg, 0.366 mmol) and cesium carbonate (157.0 mg, 0.482 mmol) in anhydrous 1,4-dioxane (10 ml) was degassed by three freeze-pump-thaw cycles. Then tris(dibenzylideneacetone)dipalladium(0) (22.5 mg, 0.0246 mmol) and a 0.1M solution of tri-tert-butylphosphine in 1,4-dioxane (0.58 ml, 0.058 mmol) was added and two more freeze-pump-thaw cycles were performed. The mixture was heated at 90° C. under nitrogen for 22 h, then filtered through glass fibre paper. The solid was washed with ethyl acetate, and the filtrates were washed with saturated aqueous NaCl (15 ml). The aqueous layer was further extracted with ethyl acetate (25 ml), and the combined extracts were dried (NaSO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 2% MeOH/CH2Cl2) to give 83.8 mg (83%) of the title compound as an orange solid: mp=124-129° C. (CH2Cl2-EtOAc-isohexane); 1H NMR (360 MHz, CDCl3) δ 2.60 (3H, s), 3.71 (5H, s), 5.46 (2H, s), 7.18 (1H, d, J=4.9 Hz), 7.27 (1H, m), 7.38 (1H, m), 7.38 (1H, s), 7.44 (1H, dd, J=4.9, 3.0 Hz), 7.63 (1H, m), 7.75 (1H, t, J=7.1 Hz), 7.83 (1H, s); MS (ES+) m/e 422 [M+H]+. Anal. Found C, 56.94; H, 4.04; N, 22.49%. C20H16FN7OS.0.08 C4H8O2 requires C, 56.96; H, 3.91; N, 22.88%.

후처리

  1. customwas degassed by three freeze-pump-thaw cycles
  2. filtrationfiltered through glass fibre paper
  3. washThe solid was washed with ethyl acetate
  4. washthe filtrates were washed with saturated aqueous NaCl (15 ml)
  5. extractionThe aqueous layer was further extracted with ethyl acetate (25 ml)
  6. dry with materialthe combined extracts were dried (NaSO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by flash chromatography (silica gel, 2% MeOH/CH2Cl2)

출처 및 근거

ORD 기록
ord-fa58322fdd624fafa3c9c5f72eef63d3
출처 데이터셋
uspto-grants-2005_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06872720B2

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