3-(4-Azidophenyl)propionic acid → 3-{4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]phenyl}propanoic acid

HRID 1520011ノート

反応式

HRID 1520011 の反応式
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].[C:15]([C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][N:18]=1)#[CH:16]>O1CCOCC1.O.C(Cl)Cl.CCCCCCC.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[NH:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]([C:15]2[N:3]=[N:2][N:1]([C:4]3[CH:5]=[CH:6][C:7]([CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[CH:8][CH:9]=3)[CH:16]=2)=[N:18]1

参加物

8

反応物 2

HCID 135816123-(4-Azidophenyl)propionic acidHCID 178437996HCID 178437996、化合物

生成物 1

HCID 679812963-{4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]phenyl}propanoic acid収率 75%

試薬・触媒・溶媒 5

HCID 24463Copper sulfate pentahydrate触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8900Heptane溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

3-(4-Azidophenyl)propanoic acid (Bachem, 672 mg; 3.5 mmol; 1.0 eq.) and 3-ethynyl-1H-indazole (500 mg; 3.5 mmol; 1.0 eq.) were dissolved in 1,4-dioxane (7.5 mL). D-(−)-isoascorbic acid sodium salt (139 mg; 0.70 mmol; 0.2 eq.) followed by a solution of copper sulfate pentahydrate (35 mg; 0.14 mmol; 0.04 eq.) in water (0.75 mL) were added. The reaction mixture was stirred at 90° C. for 48 h. Dioxane was partially removed under reduced pressure, water was added and the mixture was extracted with EtOAc (three times). Combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude obtained was sonicated in DCM (5 mL) and heptane (10 mL). The resulting solid was filtered and dried under high vacuum to afford the title compound as a brown solid (875 mg, 75%). 1H NMR (300 Mz, DMSO-d6) δ: 13.37 (brs, 1H), 9.27 (s, 1H), 8.35 (d, J=8.1 Hz, 1H), 7.95 (d, J=8.4 Hz, 2H), 7.61 (d, J=8.4 Hz, 1H), 7.49 (d, J=8.4 Hz, 2H), 7.46-7.41 (m, 1H), 7.27-7.22 (m, 1H), 2.92 (t, J=7.5 Hz, 2H), 2.60 (t, J=7.5 Hz, 2H). HPLC (Condition A): Rt 3.14 min (purity 93.5%). MS (ESI+): 334.2, MS (ESI−): 332.2.

後処理

  1. additionwere added
  2. customDioxane was partially removed under reduced pressure, water
  3. additionwas added
  4. extractionthe mixture was extracted with EtOAc (three times)
  5. washCombined organic layers were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude obtained
  10. filtrationThe resulting solid was filtered
  11. customdried under high vacuum

出典と根拠

ORDレコード
ord-add39913defc41c59b66de71a817f120
出典データセット
uspto-grants-2015_07
特許番号
US09073892B2

反応ノート

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