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 1951939노트

반응식

HRID 1951939 반응식
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]

참가 물질

4

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-43092f2ca3234d7d991593699024b864
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08404672B2

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