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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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2,4-Difluorobenzaldehyde → 9-[1-(2,4-Difluoro-benzyl)-azetidin-3-yl]-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

HRID 1190579
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HRID 1190579 반응식
[NH:1]1[CH2:4][CH:3]([C:5]2[CH:6]=[CH:7][C:8]3[O:17][CH2:16][CH2:15][C:14]4[S:13][C:12]([C:18]5[N:19]([CH:23]([CH3:25])[CH3:24])[N:20]=[CH:21][N:22]=5)=[N:11][C:10]=4[C:9]=3[CH:26]=2)[CH2:2]1.[F:27][C:28]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:29]=1[CH:30]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[F:27][C:28]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:29]=1[CH2:30][N:1]1[CH2:4][CH:3]([C:5]2[CH:6]=[CH:7][C:8]3[O:17][CH2:16][CH2:15][C:14]4[S:13][C:12]([C:18]5[N:19]([CH:23]([CH3:24])[CH3:25])[N:20]=[CH:21][N:22]=5)=[N:11][C:10]=4[C:9]=3[CH:26]=2)[CH2:2]1
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참가 물질

6

반응물 4

HCID 737702,4-DifluorobenzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 670505299-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

생성물 1

HCID 582039679-[1-(2,4-Difluoro-benzyl)-azetidin-3-yl]-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene
수율 50.4%

시약·촉매·용매 1

HCID 6212Chloroform용매

실험 절차

A mixture of 9-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (0.18 g, 0.49 mmol), 2,4-difluorobenzaldehyde (64 μL, 0.59 mmol) and 4 {acute over (Å)} molecular sieves in chloroform (7 mL) was heated to reflux for 3.5 hours. After cooling sodium triacetoxyborohydride (0.50 g, 2.36 mmol) was added and the mixture was stirred at RT overnight. Aqueous saturated sodium bicarbonate solution was added and the phases were separated. The aqueous phase was extracted with 10% MeOH/DCM (×4) and the combined organic phase was dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, 50-100% EtOAc in cyclohexane) to give 372 (122 mg, 50%). LCMS: RT=8.65 min, [M+H]+=494. 1H NMR δ (ppm) (CDCl3): 8.31 (1H, d, J=2.33 Hz), 7.90 (1H, s), 7.33 (1H, q, J=7.71 Hz), 7.14 (1H, dd, J=8.27, 2.33 Hz), 7.01 (1H, d, J=8.26 Hz), 6.86-6.74 (2H, m), 5.94-5.84 (1H, m), 4.37 (2H, t, J=5.06 Hz), 3.83-3.73 (3H, m), 3.68 (2H, s), 3.39 (2H, t, J=5.07 Hz), 3.29-3.23 (2H, m), 1.61 (6H, d, J=6.65 Hz)

후처리

  1. temperaturewas heated
  2. temperatureto reflux for 3.5 hours
  3. additionwas added
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted with 10% MeOH/DCM (×4)
  6. dry with materialthe combined organic phase was dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was purified by flash chromatography (SiO2, 50-100% EtOAc in cyclohexane)

출처 및 근거

ORD 기록
ord-548e9fce3e9e4a8994533ed97abe1201
출처 데이터셋
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08673952B2

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