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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 2385895
ノート
印刷プレビュー

反応式

HRID 2385895 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 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

生成物 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
収率 50.4%

試薬・触媒・溶媒 1

HCID 6212Chloroform溶媒

実験手順

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 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 (1 H, d, J=2.33 Hz), 7.90 (1 H, s), 7.33 (1 H, q, J=7.71 Hz), 7.14 (1 H, dd, J=8.27, 2.33 Hz), 7.01 (1 H, d, J=8.26 Hz), 6.86-6.74 (2 H, m), 5.94-5.84 (1 H, m), 4.37 (2 H, t, J=5.06 Hz), 3.83-3.73 (3 H, m), 3.68 (2 H, s), 3.39 (2 H, t, J=5.07 Hz), 3.29-3.23 (2 H, m), 1.61 (6 H, d, J=6.65 Hz)

後処理

  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)

出典と根拠

ORDレコード
ord-5d12ae120d7c4f24b05eac7eabaa49e3
出典データセット
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08263633B2

反応ノート

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