1-Hydroxybenzotriazole → N-(2-(4-(4-fluorophenyl)thiazol-2-yl)propyl)-3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzamide

HRID 1397439노트

반응식

HRID 1397439 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([CH:13]([CH3:16])[CH2:14][NH2:15])[S:11][CH:12]=2)=[CH:4][CH:3]=1.[F:17][C:18]([F:34])([F:33])[C:19]1[O:23][N:22]=[C:21]([C:24]2[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=2)[C:27](O)=[O:28])[N:20]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([CH:13]([CH3:16])[CH2:14][NH:15][C:27](=[O:28])[C:26]3[CH:30]=[CH:31][CH:32]=[C:24]([C:21]4[N:20]=[C:19]([C:18]([F:34])([F:33])[F:17])[O:23][N:22]=4)[CH:25]=3)[S:11][CH:12]=2)=[CH:6][CH:7]=1

참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 242620152-(4-(4-Fluorophenyl)thiazol-2-yl)propan-1-amineHCID 251808543-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid

생성물 1

HCID 69950153N-(2-(4-(4-fluorophenyl)thiazol-2-yl)propyl)-3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzamide수율 36%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

2-(4-(4-Fluorophenyl)thiazol-2-yl)propan-1-amine (50 mg, 0.21 mmol), 3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid (54.62 mg, 0.21 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) (81.12 mg, 0.42 mmol), and 1-hydroxybenzotriazole (HOBt) (45.74 mg, 0.39 mmol) were dissolved in dichloromethane (3 mL) at room temperature. Diisopropylethylamine (DIEA) (0.147 mL, 0.85 mmol) was then introduced at room temperature and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane (100 mL) and washed with water (1×20 mL) and brine (1×20 mL). The organic layer was then dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product, which was purified on a Teledyne ISCO automated column chromatography system (0-30% EtOAc/Hexanes) to give N-(2-(4-(4-fluorophenyl)thiazol-2-yl)propyl)-3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzamide (36 mg, 36% yield). 1H NMR (CDCl3) δ 8.50 (1h, s), 8.23 (1H, d, J=8 Hz), 8.03 (1H, 1H, d, J=8 Hz), 7.85-7.81 (3H, m), 7.58 (1H, t), 7.35 (1H, s), 7.03 (2H, m), 4.05 (1H, m), 3.65 (1H, m), 1.54 (3H, d, J=8 Hz). MS (ESI) m/z: Calculated for C22H16F4N4O2S: 476.09. found: 477.1 (M+H)+.

후처리

  1. washwashed with water (1×20 mL) and brine (1×20 mL)
  2. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto give the crude product, which
  5. customwas purified on a Teledyne ISCO automated column chromatography system (0-30% EtOAc/Hexanes)

출처 및 근거

ORD 기록
ord-36fb0540217f4a11a9c3a2149068cb42
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901156B2

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