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

HRID 2272803Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2272803
[CH2:1]([C:8]1[C:9]([O:30][C@H:31]2[C@@H:36]3[O:37]C(=O)[O:39][C@@H:35]3[C@@H:34]([O:41][CH3:42])[C:33]([CH3:44])([CH3:43])[O:32]2)=[CH:10][CH:11]=[C:12]2[C:17]=1[O:16][C:15](=[O:18])[C:14]([NH:19][C:20](=[O:29])OCC1C=CC=CC=1)=[CH:13]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.[NH:56]1[C:64]2[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=2)[CH:58]=[C:57]1C(O)=O.C(=O)([O-])[O-]>[Pd].C1COCC1.N1C=CC=CC=1.C(Cl)Cl.CO.C(Cl)Cl.C(N(CC)CC)C>[CH2:1]([C:8]1[C:9]([O:30][C@H:31]2[C@H:36]([OH:37])[C@H:35]([OH:39])[C@@H:34]([O:41][CH3:42])[C:33]([CH3:43])([CH3:44])[O:32]2)=[CH:10][CH:11]=[C:12]2[C:17]=1[O:16][C:15](=[O:18])[C:14]([NH:19][C:20]([C:57]1[NH:56][C:64]3[C:59]([CH:58]=1)=[CH:60][CH:61]=[CH:62][CH:63]=3)=[O:29])=[CH:13]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

11

Edukt 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 19660Carbonate IonHCID 72899Indole-2-carboxylic acidHCID 25140542Benzyl 8-benzyl-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-ylcarbamate

Produkt 1

HCID 25139948N-(8-benzyl-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2H-pyran-2-yloxy)-2-oxo-2H-chromen-3-yl)-1H-indole-2-carboxamideAusbeute 4,3 %

Reagenzien, Katalysatoren, Lösungsmittel 6

HCID 23938PalladiumKatalysatorHCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8471TriethylamineLösungsmittelHCID 21875418Pyridine methylene chlorideLösungsmittel

Versuchsvorschrift

Palladium on carbon (10%, 46 mg) was added to 25e (230 mg, 0.38 mmol) in anhydrous THF (2.50 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 (177 mg, 99%). EDCI (61.5 mg, 0.32 mmol) and 1H-indole-2-carboxylic acid (41.4 mg, 0.26 mmol) were added to the amine (60.0 mg, 0.13 mmol) in 30% pyridine/CH2Cl2 (3.50 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 3:1 Hexane:Ether→40:1 CH2Cl2:Acetone) to afford a yellow solid, which was used without further purification (66.2 mg, 85%). Triethylamine (150 μL) was added to the carbonate (66.2 mg, 0.11 mmol) in MeOH (2.50 mL) and CH2Cl2 (2.50 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford 26m as a colorless amorphous solid (6.50 mg, 10%, 8.4% over 3 steps): 1H NMR (CD2Cl2, 500 MHz) δ 8.68 (s, 1H), 8.62 (s, 1H), 7.63-7.61 (m, 1H), 7.47 (dd, J=5.7, 3.3 Hz, 1H), 7.16-7.10 (m, 4H), 7.10-7.04 (m, 4H), 6.99 (t, J=8.2 Hz, 1H), 6.74 (d, J=8.0 Hz, 1H), 6.43 (dd, J=8.1, 0.7 Hz, 1H), 5.31 (d, J=2.9 Hz, 1H), 4.17 (t, J=6.8 Hz, 1H), 4.01 (dd, J=8.5, 2.9 Hz, 1H), 3.90 (d, J=13.1 Hz, 2H), 3.45 (s, 3H), 3.16 (d, J=8.6 Hz, 1H), 2.43 (s, 1H), 2.21 (s, 1H), 1.25 (s, 3H), 0.95 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 166.8, 155.4, 153.8, 140.2, 131.6, 130.2, 128.0, 127.6, 127.5 (2C), 127.4 (2C), 126.9, 125.1 (2C), 115.2, 108.3 (2C), 105.8 (2C), 97.1 (2C), 83.3 (2C), 77.2, 70.2, 67.9 (2C), 65.0, 60.6, 21.9, 13.1, 13.0; IR (film) νmax 3333, 2961, 2926, 2854, 1717, 1601, 1466, 1261, 1090, 1076, 1041, 800, 750 cm−1; HRMS (ESI+) m/z: [M+Na]+ calcd for C33H32N2O8, 607.2056. found, 607.2056.

Aufarbeitung

  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 (177 mg, 99%)
  5. waitAfter 12 hours
  6. concentrationthe solvent was concentrated
  7. customthe residue purified via column chromatography (SiO2, 3:1 Hexane:Ether→40:1 CH2Cl2:Acetone)
  8. customto afford a yellow solid, which
  9. customwas used without further purification (66.2 mg, 85%)
  10. waitAfter 12 hours
  11. concentrationthe solvent was concentrated
  12. customthe residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone)

Quellen und Nachweise

ORD-Eintrag
ord-79d4422c509a4f67a3d6dc8b2f707cfb
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09120774B2

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