Diisopropylethylamine → (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-(5-methylpyridin-2-yl)acrylohydrazide

HRID 1465877ノート

反応式

HRID 1465877 の反応式
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20](O)=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH:25]([C:27]1[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][N:28]=1)[NH2:26].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>CCOC(C)=O.O>[F:11][C:9]([F:12])([F:10])[C:7]1[CH:6]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([NH:26][NH:25][C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][N:28]=3)=[O:21])[N:14]=2)[CH:4]=[C:3]([C:2]([F:24])([F:23])[F:1])[CH:8]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 41533962-Hydrazinyl-5-MethylpyridineHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

生成物 1

HCID 71492987(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-(5-methylpyridin-2-yl)acrylohydrazide収率 40%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-60 °C

実験手順

A 50-mL, 3-necked, round bottom flask, charged with a solution of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.25 g) in EtOAc (10 mL) was treated with 2-hydrazinyl-5-methylpyridine (0.97 g, 1.1 eq.). The mixture was cooled to −60° C. and treated with T3P (propyl phosphonic anhydride; 0.85 mL, 2.0 eq.) and DIPEA (0.5 mL, 4.0 eq.). The mixture was stirred for 30 min then poured into water (50 mL) and extracted with CH2Cl2 (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure (25° C., 20 mmHg) to afford a crude compound that was purified by column chromatography (SiO2, 60/120 mesh, MeOH:CH2Cl2 as mobile phase). The desired compound started eluting with 2.5% MeOH:CH2Cl2. Fractions containing the desired compound were combined and concentrated under reduced pressure to afford 0.130 g (yield: 40%) (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N′-(5-methylpyridin-2-yl)acrylohydrazide. 1H NMR (400 MHz, CDCl3) δ, 10.38 (s, exchangeable, 1H), 9.65 (s, 1H), 8.54 (s, 2H), 8.40 (s, exchangeable, 1H), 8.29 (s, 1H), 7.90 (s, 1H), 7.48-7.51 (d, J=10.4 Hz, 1H), 7.33-7.36 (dd, J=2 Hz, J=6 Hz, 1H), 6.61-6.63 (d, J=8.4 Hz, 1H), 6.20-6.23 (d, J=10.4 Hz, 1H), 2.15 (s, 3H); LCMS for C19H15F6N6O [M+H]+ 457.35. found 457.24 (RT 2.61 min, purity: 99.13%).

後処理

  1. extractionextracted with CH2Cl2 (2×50 mL)
  2. washThe combined organic layers were washed with brine (50 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure (25° C., 20 mmHg)
  6. customto afford a crude compound that
  7. customwas purified by column chromatography (SiO2, 60/120 mesh, MeOH:CH2Cl2 as mobile phase)
  8. washThe desired compound started eluting with 2.5% MeOH
  9. additionFractions containing the desired compound
  10. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-871e62925a5f492b9b0bb443c2252abd
出典データセット
uspto-grants-2015_04
特許番号
US08999996B2

反応ノート

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