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)-1h-indole-2-carboxamide

HRID 1511243Notes

Reaction equation

HRID 1511243 reaction equation
[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(=O)OCC1C=CC=CC=1)=[CH:6]2.CCN=C=NCCCN(C)C.[NH:52]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH:54]=[C:53]1[C:61]([OH:63])=O.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:12]1[C:11]([CH3:28])=[C:10]2[C:5]([CH:6]=[C:7]([NH:30][C:61]([C:53]3[NH:52][C:60]4[C:55]([CH:54]=3)=[CH:56][CH:57]=[CH:58][CH:59]=4)=[O:63])[C:8](=[O:29])[O:9]2)=[CH:4][C:3]=1[O:2][CH3:1]

Participants

11

Reactant 4

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

Product 1

HCID 25140678n-(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)-1h-indole-2-carboxamideYield 18%

Reagents, catalysts & solvents 6

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 21875418Pyridine methylene chlorideSolvent

Procedure

Palladium on carbon (10%, 15 mg) was added to 25a (74.0 mg, 0.13 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 (60.0 mg, 99%). EDCI (69.0 mg, 0.36 mmol) and 1H-indole-2-carboxylic acid (46.4 mg, 0.29 mmol) were added to the amine (60.0 mg, 0.14 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 colorless solid, which was used without further purification (68.0 mg, 85%). Triethylamine (150 μL) was added to the carbonate (68.0 mg, 0.12 mmol) in MeOH (2.5 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 26i as a colorless amorphous solid (12.6 mg, 19%, 16% over 3 steps): 1H NMR (CD2Cl2, 400 MHz) 8.29 (s, 1H), 7.63 (s, 1H), 7.45-7.39 (m, 3H), 6.92 (s, 1H), 6.85 (s, 1H), 6.19 (s, 1H), 5.09 (d, J=6.5 Hz, 1H), 4.31-4.28 (m, 1H), 4.01-3.97 (m, 1H), 3.94 (s, 3H), 3.62 (s, 1H), 3.56 (s, 3H), 3.15 (d, J=4.9 Hz, 1H), 2.46 (s, 3H), 2.36 (s, 1H), 1.38 (d, J=11.5 Hz, 3H), 1.32 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 157.6, 152.1, 148.2, 145.4, 142.2, 134.5, 129.9, 127.8, 127.7, 127.5, 127.3, 122.3, 121.2, 120.2, 115.0, 105.3, 105.1, 101.3, 81.7, 69.0, 68.0, 66.5, 59.1, 55.2, 28.7, 24.6, 24.1, 9.1; IR (film) νmax 2926, 1707, 1526, 1464, 1391, 1340, 1296, 1231, 1207, 1086, 1024, 943, 739, 700, 623 cm−1; HRMS (ESI+) m/z: [M+Na]+ calcd for C28H30N2O9, 561.1849. found, 561.1781.

Workup

  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 (60.0 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 colorless solid, which
  9. customwas used without further purification (68.0 mg, 85%)
  10. waitAfter 12 hours
  11. concentrationthe solvent was concentrated
  12. customthe residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone)

Sources & evidence

ORD record
ord-fe884813ada74dbe8521661f545040bc
Source dataset
uspto-grants-2012_07
Patent number
US08212011B2

Reaction notes

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