Trifluoroacetic acid → N-(2-aminobenzyl)-3-isobutyl-1-oxo-3-phenyl-3,4,6,7-tetrahydrofuro[3,4-c]pyridine-5(1H)-carboxamide

HRID 1747731노트

반응식

HRID 1747731 반응식
[CH2:1]([C:5]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:9]2[CH2:10][N:11]([C:14]([NH:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[NH:24]C(=O)OC(C)(C)C)=[O:15])[CH2:12][CH2:13][C:8]=2[C:7](=[O:32])[O:6]1)[CH:2]([CH3:4])[CH3:3].C(O)(C(F)(F)F)=O>ClCCl>[NH2:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH2:17][NH:16][C:14]([N:11]1[CH2:12][CH2:13][C:8]2[C:7](=[O:32])[O:6][C:5]([CH2:1][CH:2]([CH3:3])[CH3:4])([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:9]=2[CH2:10]1)=[O:15]

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 117901096Tert-butyl 2-((3-isobutyl-1-oxo-3-phenyl-1,3,4,5,6,7-hexahydrofuro[3,4-c]pyridine-5-carboxamido)methyl)phenylcarbamate

생성물 1

HCID 71610281N-(2-aminobenzyl)-3-isobutyl-1-oxo-3-phenyl-3,4,6,7-tetrahydrofuro[3,4-c]pyridine-5(1H)-carboxamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

To an ice-cold solution of tert-butyl 2-((3-isobutyl-1-oxo-3-phenyl-1,3,4,5,6,7-hexahydrofuro[3,4-c]pyridine-5-carboxamido)methyl)phenylcarbamate (62 mg, 0.119 mmol) in dichloromethane (5 mL) was added TFA (1 mL). The reaction mixture stirred at 0° C. for 5 hours and concentrated to dryness to provide crude N-(2-aminobenzyl)-3-isobutyl-1-oxo-3-phenyl-3,4,6,7-tetrahydrofuro[3,4-c]pyridine-5(1H)-carboxamide. The residue was added to a solution of 2-phenylacetic acid (32 mg, 0.238 mmol), BOP (79 mg, 0.179 mmol), and N,N′-diisopropylethylamine (62 mg, 0.477 mmol) in dichloromethane (5 mL), and stirred at room temperature for 16 hours. The crude reaction mixture was concentrated to dryness and purified by column chromatography (12 g, SiO2, 0 to 100% ethyl acetate in hexanes) to provide 3-isobutyl-1-oxo-3-phenyl-N-(2-(2-phenylacetamido)benzyl)-3,4,6,7-tetrahydrofuro[3,4-c]pyridine-5(1H)-carboxamide (66 mg, 93%) as a colorless oil: 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.81-0.98 (m, 6H), 1.65 (dd, J=11.87, 6.59 Hz, 1H), 1.73-1.84 (m, 1H), 2.24-2.47 (m, 4H), 3.30 (dt, J=13.19, 6.22 Hz, 1H), 3.52 (dt, J=13.56, 5.09 Hz, 1H), 3.75 (s, 2H), 3.91 (d, J=18.84 Hz, 1H), 4.21-4.48 (m, 2H), 5.22 (br. s., 1H), 6.97-7.09 (m, 1H), 6.99-7.10 (m, 1H), 7.18 (d, J=6.78 Hz, 1H), 7.23-7.47 (m, 9H), 7.75 (br. s., 1H), 7.96 (d, J=7.91 Hz, 1H), 9.65 (br. s., 1H); MS m/z 538 (M+H)+, 560 (M+23)+, 536 (M−H)−.

후처리

  1. concentrationconcentrated to dryness

출처 및 근거

ORD 기록
ord-4c2410902ca74feca16417a48d32567c
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09150582B2

반응 노트

불러오는 중…