Trifluoroacetic acid → 1-(4-(5-(5-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid

HRID 1951939ノート

反応式

HRID 1951939 の反応式
C([O:5][C:6]([CH:8]1[CH2:11][N:10]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:23]=[C:22]([C:24]4[C:28]([C:29]([F:32])([F:31])[F:30])=[C:27]([C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=5)[O:26][N:25]=4)[O:21][N:20]=3)=[CH:15][CH:14]=2)[CH2:9]1)=[O:7])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[N:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[C:27]1[O:26][N:25]=[C:24]([C:22]2[O:21][N:20]=[C:19]([C:16]3[CH:17]=[CH:18][C:13]([CH2:12][N:10]4[CH2:11][CH:8]([C:6]([OH:7])=[O:5])[CH2:9]4)=[CH:14][CH:15]=3)[N:23]=2)[C:28]=1[C:29]([F:31])([F:30])[F:32]

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 66678445Tert-butyl-1-(4-(5-(5-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

生成物 1

HCID 468471441-(4-(5-(5-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of tert-butyl-1-(4-(5-(5-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (previous reaction) in dichloromethane (0.5 mL) was added trifluoroacetic acid (0.5 mL), and the mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was treated with triethylamine and re-concentrated. The product mixture was purified by flash silica gel chromatography using a mixture of methanol, dichloromethane, and ammonium hydroxide (10:90:0-10:90:1-15:85:1-20:80:1) to give 1-(4-(5-(5-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid (0.007 g, 0.015 mmol) as an off-white solid. The product had an HPLC retention time=2.33 min.—Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=472.0. 1H NMR (500 MHz, methanol-d3) δ ppm 3.50 (quin, J=8.25 Hz, 1H), 4.21-4.29 (m, 4H), 4.46 (s, 2H), 7.66-7.71 (m, 3H), 8.02-8.05 (m, 1H), 8.08-8.13 (m, 1H), 8.28 (d, J=8.25 Hz, 2H), and 8.83-8.85 (m, 1H).

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was treated with triethylamine
  3. concentrationre-concentrated
  4. customThe product mixture was purified by flash silica gel chromatography
  5. additiona mixture of methanol, dichloromethane, and ammonium hydroxide (10:90:0-10:90:1-15:85:1-20:80:1)

出典と根拠

ORDレコード
ord-43092f2ca3234d7d991593699024b864
出典データセット
uspto-grants-2013_03
特許番号
US08404672B2

反応ノート

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