1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → n-(7-((2r,3r,4s,5r)-3,4-Dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2h-pyran-2-yloxy)-5-methoxy-8-methyl-2-oxo-2h-chromen-3-yl)-3',6-dimethoxybiphenyl-3-carboxamide

反応式

[CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][C@H:14]2[C@@H:19]3[O:20]C(=O)[O:22][C@@H:18]3[C@@H:17]([O:24][CH3:25])[C:16]([CH3:27])([CH3:26])[O:15]2)[C:10]([CH3:28])=[C:9]2[C:4]=1[CH:5]=[C:6]([NH:30][C:31](=[O:40])OCC1C=CC=CC=1)[C:7](=[O:29])[O:8]2.CCN=C=NCCCN(C)C.[CH3:52][O:53][C:54]1[CH:55]=[C:56]([C:60]2[C:65]([O:66][CH3:67])=[CH:64][CH:63]=[C:62](C(O)=O)[CH:61]=2)[CH:57]=[CH:58][CH:59]=1.C(=O)([O-])[O-]>[Pd].C1COCC1.N1C=CC=CC=1.C(Cl)Cl.CO.C(Cl)Cl.C(N(CC)CC)C>[OH:20][C@@H:19]1[C@H:18]([OH:22])[C@@H:17]([O:24][CH3:25])[C:16]([CH3:26])([CH3:27])[O:15][C@H:14]1[O:13][C:11]1[C:10]([CH3:28])=[C:9]2[C:4]([CH:5]=[C:6]([NH:30][C:31]([C:62]3[CH:61]=[C:60]([C:56]4[CH:57]=[CH:58][CH:59]=[C:54]([O:53][CH3:52])[CH:55]=4)[C:65]([O:66][CH3:67])=[CH:64][CH:63]=3)=[O:40])[C:7](=[O:29])[O:8]2)=[C:3]([O:2][CH3:1])[CH:12]=1

参加物

実験手順

Palladium on carbon (10%, 40 mg) was added to 25d (200 mg, 0.36 mmol) in anhydrous THF (2.40 mL) and the solution was placed under an atmosphere of H2. After 12 hours, the solution was filtered through SiO2 (1:1 CH2Cl2:Acetone) and the eluent was concentrated to afford a yellow solid, which was used without further purification (150 mg, 99%). EDCI (57.5 mg, 0.30 mmol) and 3′,6-dimethoxybiphenyl-3-carboxylic acid (62 mg, 0.24 mmol) were added to the amine (50.6 mg, 0.12 mmol) in 30% pyridine/CH2Cl2 (3.30 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 3:1 Hexane:Ether→40:1→10:1 CH2Cl2:Acetone) to afford a colorless solid, which was used without further purification (25.2 mg, 32%). Triethylamine (150 μL) was added to the carbonate (25.2 mg, 0.038 mmol) in MeOH (2.0 mL) and CH2Cl2 (2.0 mL). After 48 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford 26d as a colorless amorphous solid (17.0 mg, 70%, 22% over 3 steps): 1H NMR (CD2Cl2, 400 MHz) 9.02 (s, 1H), 8.97 (s, 1H), 8.66 (s, 1H), 7.96 (dd, J=8.6, 2.4 Hz, 1H), 7.91-7.90 (m, 1H), 7.39 (t, J=7.9 Hz, 1H), 7.16-7.11 (m, 2H), 6.96 (dd, J=8.3, 2.6 Hz), 6.85 (d, J=5.5 Hz, 1H), 5.70 (d, J=2.1 Hz, 1H), 4.36-4.33 (m, 1H), 4.27 (m, 1H), 3.99 (s, 3H), 3.93 (s, 3H), 3.88 (s, 3H), 3.62 (s, 3H), 3.41-3.38 (m, 1H), 2.24 (s, 3H), 1.41 (s, 3H), 1.19 (s, 3H); 13C NMR (CDCl3, 125 MHz) 164.2, 158.7, 158.6, 158.3, 155.3, 153.5, 148.6, 137.6, 129.9, 128.9, 128.1, 127.1, 125.1, 121.0, 119.4, 118.9, 114.2, 114.2, 112.1, 110.0, 104.9, 103.7, 96.7, 92.9, 83.2, 70.1, 67.5, 60.9, 60.8, 54.8, 54.3, 21.9, 21.4, 6.8; IR (film) νmax 3405, 2986, 2934, 1713, 1609, 1528, 1383, 1250, 1213, 1053, 999, 914, 878, 737 cm−1; HRMS (ESI+) m/z: [M+H]+ calcd for C34H37NO11, 636.2445. found, 636.2482.

後処理

filtrationthe solution was filtered through SiO2 (1:1 CH2Cl2:Acetone)
concentrationthe eluent was concentrated
customto afford a yellow solid, which
customwas used without further purification (150 mg, 99%)
waitAfter 12 hours
concentrationthe solvent was concentrated
customthe residue purified via column chromatography (SiO2, 3:1 Hexane:Ether→40:1→10:1 CH2Cl2:Acetone)
customto afford a colorless solid, which
customwas used without further purification (25.2 mg, 32%)
waitAfter 48 hours
concentrationthe solvent was concentrated
customthe residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone)

出典と根拠

ORDレコード: ord-cea50377635141d9a4fb05d941185c82
出典データセット: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US08212011B2

反応ノート

読み込み中…

反応式

参加物

反応物 4

生成物 1

試薬・触媒・溶媒 6

実験手順

後処理

出典と根拠

反応ノート