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

HRID 1747731ノート

反応式

HRID 1747731 の反応式
[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]

参加物

4

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

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)−.

後処理

  1. concentrationconcentrated to dryness

出典と根拠

ORDレコード
ord-4c2410902ca74feca16417a48d32567c
出典データセット
uspto-grants-2015_10
特許番号
US09150582B2

反応ノート

読み込み中…