1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(7-((2S,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2H-pyran-2-yloxy)-6-methoxy-8-methyl-2-oxo-2H-chromen-3-yl)-3',6-dimethoxybiphenyl-3-carboxamide

HRID 1511237ノート

反応式

HRID 1511237 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([CH3:28])[C:12]=1[O:13][C@H:14]1[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]1)[O:9][C:8](=[O:29])[C:7]([NH:30][C:31](=[O:40])OCC1C=CC=CC=1)=[CH:6]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(N(CC)CC)C>[OH:20][C@@H:19]1[C@H:18]([OH:22])[C@@H:17]([O:24][CH3:25])[C:16]([CH3:27])([CH3:26])[O:15][C@H:14]1[O:13][C:12]1[C:11]([CH3:28])=[C:10]2[C:5]([CH:6]=[C:7]([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:8](=[O:29])[O:9]2)=[CH:4][C:3]=1[O:2][CH3:1]

参加物

10

反応物 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 19660Carbonate IonHCID 25140397Benzyl 6-methoxy-7-((3aR,4S,7R,7aR)-7-methoxy-6,6-dimethyl-2-oxotetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yloxy)-8-methyl-2-oxo-2H-chromen-3-ylcarbamateHCID 549124263',6-Dimethoxy-(1,1'-biphenyl)-3-carboxylic acid

生成物 1

HCID 25139812N-(7-((2S,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2H-pyran-2-yloxy)-6-methoxy-8-methyl-2-oxo-2H-chromen-3-yl)-3',6-dimethoxybiphenyl-3-carboxamide収率 3.5%

試薬・触媒・溶媒 5

HCID 23938Palladium触媒HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒HCID 21875418Pyridine methylene chloride溶媒

実験手順

Palladium on carbon (10%, 20.0 mg) was added to 25a (100 mg, 0.18 mmol) in anhydrous THF (5.00 mL) and the solution was placed under an atmosphere of H2. After 6.5 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 (56.0 mg, 75%). EDCI (21.4 mg, 0.11 mmol) and 3′,6-dimethoxybiphenyl-3-carboxylic acid (23.1 mg, 0.089 mmol) were added to the amine (18.7 mg, 0.045 mmol) in 30% pyridine/CH2Cl2 (0.70 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford a colorless solid, which was used without further purification (10.5 mg, 36%). Triethylamine (150 μL) was added to the carbonate (10.4 mg, 0.016 mmol) in MeOH (2.50 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 20:1; CH2Cl2:MeOH) to afford 26a as a colorless amorphous solid (2.00 mg, 20%, 5% over 3 steps): 1H NMR (CDCl3, 500 MHz) 8.73 (s, 1H), 8.70 (d, J=5.4 Hz, 1H), 7.84 (td, J=6.2, 2.4 Hz, 1H), 7.82 (s, 1H), 7.30 (t, J=8.0 Hz, 1H), 7.06 (d, J=7.8 Hz, 1H), 7.03-7.00 (m, 2H), 6.88-6.86 (m, 1H), 6.81 (s, 1H), 4.99 (d, J=6.6 Hz, 1H), 4.24 (t, J=4.2 Hz, 1H), 4.00 (dd, J=6.5, 3.7 Hz, 1H), 3.90 (s, 3H), 3.86 (s, 3H), 3.83 (s, 3H), 3.80 (d, J=7.4 Hz, 1H), 3.45 (s, 3H), 3.08 (d, J=4.7 Hz, 1H), 2.67 (s, 1H), 2.42 (s, 3H), 1.28 (d, J=8.1 Hz, 3H), 1.18 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 164.6, 158.9, 158.3, 158.2, 148.2, 145.6, 142.5, 137.5, 130.1, 129.0, 128.2, 127.2, 124.9, 122.5, 122.2, 121.2, 121.0, 115.1, 144.2, 112.1, 110.0, 105.4, 101.3, 81.7, 76.8, 69.0, 68.0, 59.1, 55.3, 54.9, 54.3, 28.3, 28.2, 9.1; IR (film) νmax 2961, 2928, 1713, 1670, 1601, 1464, 1383, 1261, 1094, 1022, 798, 700 cm−1; HRMS (ESI+) m/z: [M+H]+ calcd for C34H37NO11, 636.2445. found, 636.2477.

後処理

  1. filtrationthe solution was filtered through SiO2 (1:1 CH2Cl2:Acetone)
  2. concentrationthe eluent was concentrated
  3. customto afford a yellow solid, which
  4. customwas used without further purification (56.0 mg, 75%)
  5. waitAfter 12 hours
  6. concentrationthe solvent was concentrated
  7. customthe residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone)
  8. customto afford a colorless solid, which
  9. customwas used without further purification (10.5 mg, 36%)
  10. waitAfter 12 hours
  11. concentrationthe solvent was concentrated
  12. customthe residue purified via column chromatography (SiO2, 20:1; CH2Cl2:MeOH)

出典と根拠

ORDレコード
ord-d87471e3bd4348e289fa5e9fc1e47cf8
出典データセット
uspto-grants-2012_07
特許番号
US08212011B2

反応ノート

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