1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → n-(7-((2r,3r,4s,5r)-3,4-Dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2h-pyran-2-yloxy)-2-oxo-8-phenyl-2h-chromen-3-yl)-1h-indole-2-carboxamide

HRID 2272804Notes

Reaction equation

HRID 2272804 reaction equation
[CH3:1][O:2][C@H:3]1[C:8]([CH3:10])([CH3:9])[O:7][C@@H:6]([O:11][C:12]2[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:20]3[C:15]([CH:16]=[C:17]([NH:29][C:30](=[O:39])OCC4C=CC=CC=4)[C:18](=[O:28])[O:19]3)=[CH:14][CH:13]=2)[C@@H:5]2[O:40]C(=O)[O:42][C@H:4]12.CCN=C=NCCCN(C)C.[NH:55]1[C:63]2[C:58](=[CH:59][CH:60]=[CH:61][CH:62]=2)[CH:57]=[C:56]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:40][C@@H:5]1[C@H:4]([OH:42])[C@@H:3]([O:2][CH3:1])[C:8]([CH3:10])([CH3:9])[O:7][C@H:6]1[O:11][C:12]1[C:21]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:20]2[C:15]([CH:16]=[C:17]([NH:29][C:30]([C:56]3[NH:55][C:63]4[C:58]([CH:57]=3)=[CH:59][CH:60]=[CH:61][CH:62]=4)=[O:39])[C:18](=[O:28])[O:19]2)=[CH:14][CH:13]=1

Participants

11

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 19660Carbonate IonHCID 72899Indole-2-carboxylic acidHCID 25138941Benzyl 7-((3aR,4R,7R,7aR)-7-methoxy-6,6-dimethyl-2-oxotetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yloxy)-2-oxo-8-phenyl-2H-chromen-3-ylcarbamate

Product 1

HCID 25140680n-(7-((2r,3r,4s,5r)-3,4-Dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2h-pyran-2-yloxy)-2-oxo-8-phenyl-2h-chromen-3-yl)-1h-indole-2-carboxamideYield 9.1%

Reagents, catalysts & solvents 6

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

Procedure

Palladium on carbon (10%, 14 mg) was added to 25f (68.0 mg, 0.12 mmol) in anhydrous THF (800 μL) 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 (52.0 mg, 99%). EDCI (18.5 mg, 0.096 mmol) and 1H-indole-2-carboxylic acid (12.4 mg, 0.077 mmol) were added to the amine (17.5 mg, 0.039 mmol) in 30% pyridine/CH2Cl2 (1.10 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 (8.20 mg, 36%). Triethylamine (150 μL) was added to the carbonate (8.2 mg, 0.014 mmol) in MeOH (1.00 mL) and CH2Cl2 (1.00 mL). After 48 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford 26n as a colorless amorphous solid (4.00 mg, 51%, 18% over 3 steps): 1H NMR (CD2Cl2, 500 MHz) δ 9.23 (s, 1H), 8.80 (s, 1H), 8.67 (s, 1H), 7.71 (dd, J=8.0, 0.7 Hz, 1H), 7.57 (d, J=8.8 Hz, 1H), 7.51-7.48 (m, 3H), 7.46-7.44 (m, 1H), 7.37-7.32 (m, 4H), 7.19-7.17 (m, 2H), 5.53 (d, J=2.4 Hz, 1H), 3.86 (s, 1H), 3.76-3.73 (m, 2H), 3.51 (s, 3H), 3.23 (d, J=9.1 Hz, 1H), 2.41 (s, 1H), 1.34 (s, 3H), 1.05 (s, 3H); 13C NMR (CD2Cl2, 125 MHz) δ 159.1, 157.9, 154.5, 147.3, 136.0 (2C), 130.7 (2C), 129.8, 129.2, 127.3, 127.1, 127.0, 126.9, 124.5, 122.8, 121.6, 121.2, 120.3, 113.7, 111.4, 111.1, 103.1 (2C), 97.5, 83.2, 77.7, 70.1, 67.5, 60.8, 21.9, 21.7; IR (film) νmax 3427, 2961, 2924, 2853, 2062, 1643, 1614, 1537, 1362, 1236, 1094, 1041, 962, 791, 739, 698 cm−1; HRMS (ESI+) m/z: [M+Na]+ calcd for C32H30N2O8, 593.1900. found, 593.1890.

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 (52.0 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 (8.20 mg, 36%)
  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-db0071d09ff047e9a38af064bb15f2a0
Source dataset
uspto-grants-2015_09
Patent number
US09120774B2

Reaction notes

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