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)-1H-indole-2-carboxamide

HRID 2272805Notes

Reaction equation

HRID 2272805 reaction equation
[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.[NH:51]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[CH:53]=[C:52]1C(O)=O.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]([CH3:39])([CH3:38])[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:52]3[NH:51][C:59]4[C:54]([CH:53]=3)=[CH:55][CH:56]=[CH:57][CH:58]=4)=[O:24])[C:10](=[O:13])[O:11]2)=[CH:6][CH:5]=1

Participants

10

Reactant 4

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

Product 1

HCID 25140681N-(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)-1H-indole-2-carboxamideYield 8%

Reagents, catalysts & solvents 5

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

Procedure

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 (28.3 mg, 0.15 mmol) and 1H-indole-2-carboxylic acid (19.0 mg, 0.12 mmol) were added to the amine (24.0 mg, 0.059 mmol) in 30% pyridine/CH2Cl2 (1.63 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford an colorless foam, which was used without further purification (23.8 mg, 73%). Triethylamine (150 μL) was added to the carbonate (14.1 mg, 0.026 mmol) in MeOH (1.50 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford 26p as a yellow amorphous solid (5.00 mg, 37%, 27% over 3 steps): 1H NMR (CD2Cl2, 500 MHz) δ 8.65 (s, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.41 (d, J=8.5 Hz, 1H), 7.33 (d, J=8.5 Hz, 1H), 7.23 (t, J=7.8 Hz, 1H), 7.20 (d, J=8.5 Hz, 2H), 7.13 (s, 2H), 7.07 (t, J=7.5 Hz, 1H), 5.46 (d, J=2.0 Hz, 1H), 4.07 (dd, J=9.3, 3.5 Hz, 1H), 4.04 (t, J=3.5 Hz, 1H), 3.51 (s, 3H), 3.25 (d, J=7.2 Hz, 1H), 2.78 (q, J=7.0 Hz, 2H), 1.27 (s, 3H), 1.10 (t, J=7.5 Hz, 3H), 1.06 (s, 3H); 13C NMR (CD2Cl2, 125 MHz) δ 158.4, 157.3, 154.2, 146.8, 135.3, 128.1, 125.5, 124.0, 123.0, 123.0, 122.8, 120.1, 119.5, 118.7, 118.2, 112.0, 110.1, 109.7, 102.4, 97.0, 82.1, 76.5, 69.3, 66.4, 26.7, 20.3, 14.3, 11.4; IR (film) νmax 3435, 3416, 2974, 2935, 2469, 2359, 2339, 1715, 1651, 1520, 1456, 1435, 1379, 1354, 1259, 1180, 1113, 1088, 1026, 997, 962, 798, 739 cm−1; HRMS (ESI+) m/z: [M+Na]+ calcd for C28H30N2O8, 545.1900. found, 545.1909.

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 (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 an colorless foam, which
  9. customwas used without further purification (23.8 mg, 73%)
  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-0534af5c7e814c0eae3d83784092b1b7
Source dataset
uspto-grants-2015_09
Patent number
US09120774B2

Reaction notes

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