Hydrochloric Acid → 1-[1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-[1,2,3]triazol-4-yl]-3-(2-chloro-phenyl)-propane-1,3-dione

HRID 2251986

反応式

HRID 2251986 の反応式
C([N-]C(C)C)(C)C.[Li+].[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16](=[O:18])[CH3:17].CON(C)[C:22]([C:24]1[N:25]=[N:26][N:27]([CH2:35][C:36]2[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[C:38]([C:46]([F:49])([F:48])[F:47])[CH:37]=2)[C:28]=1[C:29]1[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=1)=[O:23].Cl>C1COCC1>[F:45][C:42]([F:43])([F:44])[C:40]1[CH:41]=[C:36]([CH:37]=[C:38]([C:46]([F:47])([F:49])[F:48])[CH:39]=1)[CH2:35][N:27]1[C:28]([C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)=[C:24]([C:22](=[O:23])[CH2:17][C:16]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[Cl:9])=[O:18])[N:25]=[N:26]1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 72864Ethanone, 1-(2-chlorophenyl)-HCID 2724682Lithium diisopropylamideHCID 86601237HCID 86601237、化合物

生成物 1

HCID 866012491-[1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-[1,2,3]triazol-4-yl]-3-(2-chloro-phenyl)-propane-1,3-dione収率 69%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Add lithium diisopropylamide (6 mL, 1.0 M in THF) to a solution of 1-(2-chloro-phenyl)-ethanone (0.929 g, 6.01 mmol) in THF (10 mL) at −78° C. and stir for 30 min. To the above enolate solution at −78° C., add a solution of 1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid methoxy-N-methyl-amide (1.29 g, 2.81 mmol) in THF (15 mL) via cannula. Warm solution to 70° C. and stir for 4 hours, than add 1N HCl (6 mL) and stir for an additional 30 min. Concentrate the mixture in vacuo to ¼ volume, dilute with EtOAc (60 mL) and wash with water (30 mL), saturated NaHCO3 (30 mL), and brine (30 mL). Dry, filter, and concentrate the organic phase and purify the crude material by flash chromatography using a linear gradient of 20% to 80% EtOAc/hexanes to give the title compound (1.07 g, 69%) as an orange foam. MS (IS) 553.2 (M+1), MS (ES−) 551.2 (M−1). 1H NMR (400 MHz, CDCl3): δ 15.5 (m, 1H), 7.78 (dd, 1H, J=1.3, 4.8), 8.54 (d, 1H, J=2.2), 7.81 (s, 1H), 7.64 (dd, 1H, J=2.0, 7.7), 7.57 (dt, 1H, J=2.0, 7.9), 7.44 (m, 4H), 7.38 (dt, 1H, J=1.8, 7.5), 7.33 (dt, 1H, J=1.5, 7.5), 7.19 (s, 1H), 5.59 (s, 2H).

後処理

  1. stirringWarm solution to 70° C. and stir for 4 hours
  2. stirringstir for an additional 30 min
  3. concentrationConcentrate the mixture in vacuo
  4. additiondilute with EtOAc (60 mL)
  5. washwash with water (30 mL), saturated NaHCO3 (30 mL), and brine (30 mL)
  6. customDry
  7. filtrationfilter
  8. concentrationconcentrate the organic phase
  9. custompurify the crude material by flash chromatography

出典と根拠

ORDレコード
ord-5d45546754bb42fcb64387fa4583a837
出典データセット
uspto-grants-2008_01
特許番号
US07320994B2

関連ノート

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