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

HRID 2272798
ノート
印刷プレビュー

反応式

HRID 2272798 の反応式
[CH2:1]([C:3]1[C:4]([O:25][C@H:26]2[C@@H:31]3[O:32]C(=O)[O:34][C@@H:30]3[C@@H:29]([O:36][CH3:37])[C:28]([CH3:39])([CH3:38])[O:27]2)=[CH:5][CH:6]=[C:7]2[C:12]=1[O:11][C:10](=[O:13])[C:9]([NH:14][C:15](=[O:24])OCC1C=CC=CC=1)=[CH:8]2)[CH3:2].CCN=C=NCCCN(C)C.[CH3:51][O:52][C:53]1[CH:54]=[C:55]([C:59]2[C:64]([O:65][CH3:66])=[CH:63][CH:62]=[C:61](C(O)=O)[CH:60]=2)[CH:56]=[CH:57][CH:58]=1.C(=O)([O-])[O-]>[Pd].C1COCC1.N1C=CC=CC=1.C(Cl)Cl.CO.C(N(CC)CC)C>[OH:32][C@@H:31]1[C@H:30]([OH:34])[C@@H:29]([O:36][CH3:37])[C:28]([CH3:38])([CH3:39])[O:27][C@H:26]1[O:25][C:4]1[C:3]([CH2:1][CH3:2])=[C:12]2[C:7]([CH:8]=[C:9]([NH:14][C:15]([C:61]3[CH:60]=[C:59]([C:55]4[CH:56]=[CH:57][CH:58]=[C:53]([O:52][CH3:51])[CH:54]=4)[C:64]([O:65][CH3:66])=[CH:63][CH:62]=3)=[O:24])[C:10](=[O:13])[O:11]2)=[CH:6][CH:5]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

10

反応物 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 19660Carbonate IonHCID 25140543Benzyl 8-ethyl-7-((3aR,4R,7R,7aR)-7-methoxy-6,6-dimethyl-2-oxotetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yloxy)-2-oxo-2H-chromen-3-ylcarbamateHCID 549124263',6-Dimethoxy-(1,1'-biphenyl)-3-carboxylic acid

生成物 1

HCID 25139945
N-(7-((2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2H-pyran-2-yloxy)-8-ethyl-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%, 12 mg) was added to 25h (121 mg, 0.22 mmol) in anhydrous THF (5.00 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 (90.0 mg, 99%). EDCI (46.2 mg, 0.24 mmol) and 3′,6-dimethoxybiphenyl-3-carboxylic acid (43.9 mg, 0.19 mmol) were added to the amine (39.0 mg, 0.096 mmol) in 30% pyridine/CH2Cl2 (2.65 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 (39.1 mg, 66%). Triethylamine (150 μL) was added to the carbonate (13.0 mg, 0.020 mmol) in MeOH (1.5 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford 26h as a colorless amorphous solid (4.10 mg, 33%, 22% over 3 steps): 1H NMR (CD2Cl2, 500 MHz) δ 8.70 (s, 1H), 8.61 (s, 1H), 7.83 (dd, J=8.5, 2.5 Hz, 1H), 7.78 (d, J=2.5 Hz, 1H), 7.31 (d, J=9.0 Hz, 1H), 7.27 (t, J=7.8 Hz, 1H), 7.17 (d, J=8.5 Hz, 1H), 7.03-6.99 (m, 3H), 6.85-6.82 (m, 1H), 5.49 (d, J=1.5 Hz, 1H), 4.15 (t, J=8.5 Hz, 1H), 4.14 (d, J=8.5 Hz, 1H), 3.90 (s, 2H), 3.87 (s, 3H), 3.81 (s, 3H), 3.28 (s, 3H), 3.27 (d, J=8.5 Hz, 1H), 2.76 (q, J=4.5 Hz, 2H), 1.29 (s, 3H), 1.09 (t, J=7.4 Hz, 3H), 1.08 (s, 3H); 13C NMR (CD2Cl2, 125 MHz) δ 164.5, 159.0, 158.6, 158.5, 155.1, 147.9, 138.1, 130.1, 129.1, 128.3, 127.4, 125.4, 125.2, 123.1, 121.4, 121.2, 119.4, 114.5, 113.5, 112.1, 110.8, 110.2, 97.6, 83.4, 77.7, 70.6, 67.8, 61.0, 55.1, 54.5, 28.2, 21.6, 15.6, 12.9; IR (film) νmax 3404, 2968, 2934, 2359, 2341, 1715, 1605, 1524, 1504, 1367, 1244, 1101, 1024, 995, 960, 800 cm−1; HRMS (ESI+) m/z: [M+H]+ calcd for C34H37NO10, 620.2496. found, 620.2507.

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 (90.0 mg, 99%)
  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 (39.1 mg, 66%)
  10. waitAfter 12 hours
  11. concentrationthe solvent was concentrated
  12. customthe residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone)

出典と根拠

ORDレコード
ord-fde47434f8bf47049b6a9f64ea247b6e
出典データセット
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09120774B2

反応ノート

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