Pyridine → HCID 72705359, compound

HRID 2176208Notes

Reaction equation

HRID 2176208 reaction equation
C([Si](C)(C)[O:6][C@@H:7]1[CH2:32][CH2:31][CH:30]=[CH:29][C:28]2=[CH:33][C:24](=[CH:25][CH:26]=[CH:27]2)[C@@H:23]([CH3:34])[NH:22][C:21](=[O:35])[C@H:20]2[NH:36][N:16]([CH2:17][CH2:18][CH2:19]2)[C:15](=[O:37])[C@H:14]([CH3:38])[NH:13][C:12](=[O:39])[C@H:11]([CH:40]([CH3:42])[CH3:41])[O:10][C:9](=[O:43])[C@@H:8]1[CH3:44])(C)(C)C.N1C=CC=CC=1>C(OCC)(=O)C.[Pd]>[OH:6][C@@H:7]1[CH2:32][CH2:31][CH2:30][CH2:29][C:28]2=[CH:33][C:24](=[CH:25][CH:26]=[CH:27]2)[C@@H:23]([CH3:34])[NH:22][C:21](=[O:35])[C@H:20]2[NH:36][N:16]([CH2:17][CH2:18][CH2:19]2)[C:15](=[O:37])[C@H:14]([CH3:38])[NH:13][C:12](=[O:39])[C@H:11]([CH:40]([CH3:42])[CH3:41])[O:10][C:9](=[O:43])[C@@H:8]1[CH3:44]

Participants

5

Reactant 2

HCID 1049PyridineHCID 131732990HCID 131732990, compound

Product 1

HCID 72705359HCID 72705359, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

To (E)-(2R,5S,11S,14S,17R,18R)-18-(tert-butyl-dimethyl-silanyloxy)-14-isopropyl-2,11,17-trimethyl-15-oxa-3,9,12,28-tetraaza-tricyclo[21.3.1.1*5,9*]octacosa-1(26),21,23(27),24-tetraene-4,10,13,16-tetraone (50 mg, 0.08 mmol) in ethyl acetate (10 mL) at room temperature was added 10% palladium on carbon (50 mg). The system was purged with hydrogen gas and stirred vigorously for 16 h. The reaction mixture was filtered through Celite and the filter pad washed with methanol. The filtrate was concentrated in vacuo. The ensuing residue was dissolved in anhydrous tetrahydrofuran (5 mL) and transferred to a polypropylene vial. At room temperature hydrogen fluoride.pyridine (1.3 mL, 15.2 mmol) was added to the reaction mixture followed by stirring for 3 h. The reaction was diluted with ethyl acetate and quenched by cautious addition of saturated aqueous ammonium chloride. The organic layer was separated, dried through a hydrophobic frit and concentrated in vacuo. The residue was purified by silica gel chromatography using ethyl acetate/acetone 5/1 to afford the title compound as a white solid. This was further purified by triturating with diethyl ether, filtering and drying the solid in vacuo (20 mg, 48%, 2 steps). 1H NMR (300 MHz, CD3CN) 0.90-1.00 (m, 6H), 1.24-1.30 (m, 6H), 1.43 (d, J=6.9 Hz, 3H), 1.32-2.08 (m, 11H), 2.45-2.81 (m, 4H), 3.23-3.36 (m, 1H), 3.47-3.59 (m, 1H), 3.67 (d, J=10.3 Hz, 1H), 4.02 (d, J=11.8 Hz, 1H), 4.29 (d, J=13.8 Hz, 1H), 4.75 (d, J=5.4 Hz, 1H), 4.95-5.08 (m, 1H), 5.16-5.29 (m, 1H), 7.03-7.29 (m, 6H). LCMS (m/z)=545.3 [M+H], Tr=2.15 min.

Workup

  1. customThe system was purged with hydrogen gas
  2. filtrationThe reaction mixture was filtered through Celite
  3. washthe filter pad washed with methanol
  4. concentrationThe filtrate was concentrated in vacuo
  5. dissolutionThe ensuing residue was dissolved in anhydrous tetrahydrofuran (5 mL)
  6. customAt room temperature
  7. stirringby stirring for 3 h
  8. customquenched by cautious addition of saturated aqueous ammonium chloride
  9. customThe organic layer was separated
  10. customdried through a hydrophobic frit
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f5d45d74d8844e4784e11b0273b93600
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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