Pyridine → HCID 76901900, compound

HRID 1174355Notes

Reaction equation

HRID 1174355 reaction equation
[N:1]([C@@H:4]([C@H:46]1[CH2:50][CH2:49][O:48][CH2:47]1)[C:5]([NH:7][C@@H:8]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C@@H:9]([OH:38])[CH2:10][C@@H:11]([NH:25][C:26](=[O:37])[C@H:27]([C:33]([CH3:36])([CH3:35])[CH3:34])[NH:28]C(OC)=O)[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:15][CH:14]=1)=[O:6])=[N+]=[N-].N1C=CC=CC=1.Cl[C:58]([O:60][CH3:61])=[O:59]>CO.C(OCC)(=O)C.[Pd]>[CH3:61][O:60][C:58](=[O:59])[NH:1][C@@H:4]([C@H:46]1[CH2:50][CH2:49][O:48][CH2:47]1)[C:5](=[O:6])[NH:7][C@@H:8]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C@@H:9]([OH:38])[CH2:10][C@H:11]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:15][CH:14]=1)[NH:25][C:26](=[O:37])[C@H:27]([C:33]([CH3:34])([CH3:35])[CH3:36])[NH:28][C:58](=[O:59])[O:60][CH3:61]

Participants

7

Reactant 3

HCID 1049PyridineHCID 6586Methyl chloroformateHCID 86599581HCID 86599581, compound

Product 1

HCID 76901900HCID 76901900, compoundYield 91.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of the product of Example 142A (0.038 g, 0.055 mmol) in a mixture of methanol (0.40 mL) and ethyl acetate (0.40 mL) was added 10% Pd on C (0.038 g), and the reaction was stirred under an atmosphere of hydrogen (balloon pressure) for 2 hours. The mixture was filtered through celite and the solvent was evaporated. The residue was dissolved in dichloromethane (0.40 mL) and pyridine (0.007 mL, 0.087 mmol) and methyl chloroformate (0.004 mL, 0.052 mmol) were added and the mixture was stirred at room temperature for 1 hour. The reaction was diluted with ethyl acetate and the organic layer was washed with dilute NaHCO3, and brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with a gradient starting with chloroform and ending with 5% methanol in ethyl acetate to give the title compound (0.017 g, 43% yield). 1H NMR (300 MHz, MeOH-d4), δ ppm 0.87 (s, 9 H), 1.51-1.66 (m, 4 H), 2.31-2.43 (m, 1 H), 2.66 (dd, J=13.4, 9.0 Hz, 1 H), 2.83-2.96 (m, 3 H), 3.44 (dd, J=6.4, 9.0 Hz, 1 H), 3.52 (s, 3 H), 3.55-3.85 (m, 5 H), 3.65 (s, 3 H), 3.91 (d, J=9.6 Hz, 1 H), 4.24-4.30 (m, 1 H), 4.34-4.42 (m, 1 H), 7.11-7.35 (m, 8 H), 7.78-7.90 (m, 4 H), 8.57 (m, 1 H).

Workup

  1. filtrationThe mixture was filtered through celite
  2. customthe solvent was evaporated
  3. dissolutionThe residue was dissolved in dichloromethane (0.40 mL)
  4. stirringthe mixture was stirred at room temperature for 1 hour
  5. washthe organic layer was washed with dilute NaHCO3, and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed on silica gel eluting with a gradient

Sources & evidence

ORD record
ord-d1a921a188ed44a1b53277a28c81b102
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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