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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)-5-methoxy-8-methyl-2-oxo-2h-chromen-3-yl)-1h-indole-2-carboxamide

HRID 1511246
Notes
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Reaction equation

HRID 1511246 reaction equation
[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)[O:32]CC1C=CC=CC=1)[C:7](=[O:29])[O:8]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]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>[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:53]3[NH:52][C:60]4[C:55]([CH:54]=3)=[CH:56][CH:57]=[CH:58][CH:59]=4)=[O:32])[C:7](=[O:29])[O:8]2)=[C:3]([O:2][CH3:1])[CH:12]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

11

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 19660Carbonate IonHCID 72899Indole-2-carboxylic acidHCID 25138940Benzyl 5-methoxy-7-((3aR,4R,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 25139947
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)-1h-indole-2-carboxamide
Yield 5.1%

Reagents, catalysts & solvents 6

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

Procedure

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 1H-indole-2-carboxylic acid (38.7 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, 40:1 CH2Cl2:Acetone) to afford a colorless solid, which was used without further purification (26.3 mg, 39%). Triethylamine (150 μL) was added to the carbonate (26.3 mg, 0.047 mmol) in MeOH (2.00 mL) and CH2Cl2 (2.00 mL). After 48 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford 26l as a colorless amorphous solid (6.60 mg, 26%, 10% over 3 steps): 1H NMR (CD2Cl2, 400 MHz) 9.26 (s, 1H), 8.96 (s, 1H), 8.68 (s, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.52 (d, J=8.3 Hz, 1H), 7.38-7.34 (m, 1H), 7.22-7.16 (m, 1H), 6.84 (s, 1H), 6.00 (s, 1H), 5.65 (d, J=1.7 Hz, 1H), 4.26-4.21 (m, 2H), 3.96 (s, 3H), 3.59 (s, 3H), 3.35 (d, J=8.6 Hz, 1H), 2.25 (s, 3H), 1.53 (s, 3H), 1.20 (s, 3H); 13C NMR (CDCl3, 125 MHz) 165.1, 157.4, 156.5, 149.7, 136.7, 134.7, 127.7, 125.3, 122.5, 121.1, 120.0, 111.9, 104.6, 103.8, 97.7, 94.0, 84.3, 84.2, 82.6, 69.6, 69.1, 66.1, 62.2, 62.0, 59.7, 23.1, 22.7, 14.2; IR (film) νmax 3389, 2924, 2853, 1697, 1605, 1535, 1460, 1340, 1211, 1101, 1088, 962, 729 cm−1; HRMS (ESI+) m/z: [M+H]+ calcd for C28H30N2O9, 539.2030. found, 539.2056.

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 (150 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 (26.3 mg, 39%)
  10. waitAfter 48 hours
  11. concentrationthe solvent was concentrated
  12. customthe residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone)

Sources & evidence

ORD record
ord-0fcb6eb7cd6a4265a4f8ee3f493dbdd0
Source dataset
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08212011B2

Reaction notes

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