Diisopropylethylamine → (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N-((2-methylpyrimidin-5-yl)methyl)acrylamide

HRID 1486976ノート

反応式

HRID 1486976 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]([OH:22])=O)[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C.[CH3:52][C:53]1[N:58]=[CH:57][C:56]([CH2:59][NH2:60])=[CH:55][N:54]=1>ClCCl.CO.C(OCC)(=O)C>[F:12][C:9]([F:11])([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:60][CH2:59][C:56]3[CH:55]=[N:54][C:53]([CH3:52])=[N:58][CH:57]=3)=[O:22])[N:14]=2)[CH:4]=[C:3]([C:2]([F:24])([F:23])[F:1])[CH:8]=1

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 21294601(2-Methylpyrimidin-5-yl)methanamineHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

生成物 1

HCID 71493803(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N-((2-methylpyrimidin-5-yl)methyl)acrylamide収率 99.3%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

In a 25 mL 3N round-bottomed flask equipped with nitrogen inlet, (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (4) (0.1 g, 1.0 eq.) was charged along with dichloromethane (5.0 mL, 50 V) and ethyl acetate (5.0 mL, 50 V). The reaction mixture was cooled to 0° C. and then added T3P (50% in ethyl acetate) (0.214 g, 1.2 eq.) followed by DIPEA (0.073 g, 2.0 eq.) and (2-methylpyrimidin-5-yl)methanamine (0.038 g, 1.1 eq.). The clear reaction mixture was stirred at 0° C. for 30 min. The progress of the reaction was followed by TLC analysis on silica gel with 10% Methanol in dichloromethane as mobile phase and visualization with UV. Reaction mixture was quenched in 30 mL ice-water slurry. Organic layer was separated and aqueous layer was extracted with dichloromethane (2×20 mL) to ensure complete extraction. The organic layer was washed with brine solution and dried over anhydrous Na2SO4 and concentrated by rotary evaporation under reduced pressure (35° C., 20 mm Hg) to afford 0.129 g of crude compound. (cis: 81.98%; trans: not detected; unreacted SM: 13.95%).

後処理

  1. customIn a 25 mL 3N round-bottomed flask equipped with nitrogen inlet
  2. customReaction mixture
  3. customwas quenched in 30 mL ice-water slurry
  4. customOrganic layer was separated
  5. extractionaqueous layer was extracted with dichloromethane (2×20 mL)
  6. extractionextraction
  7. washThe organic layer was washed with brine solution
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated by rotary evaporation under reduced pressure (35° C., 20 mm Hg)

出典と根拠

ORDレコード
ord-577837dcc5154646a9188c90d1d43b5e
出典データセット
uspto-grants-2016_08
特許番号
US09428490B2

反応ノート

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