HCID 57550073, compound → HCID 57468384, compound

HRID 1895708Notes

Reaction equation

HRID 1895708 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]4[CH:32]=[CH:31][C:30]([CH:33]=[C:34]([CH3:36])[CH3:35])=[CH:29][CH:28]=4)=[O:25])[CH2:20][CH2:19]3)=[CH:13][C:12]2=[O:37])=[CH:7][CH:6]=1)(=[O:4])=[O:3]>[Pd].CO.CN(C=O)C.C(Cl)Cl>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]4[CH:28]=[CH:29][C:30]([CH2:33][CH:34]([CH3:35])[CH3:36])=[CH:31][CH:32]=4)=[O:25])[CH2:20][CH2:19]3)=[CH:13][C:12]2=[O:37])=[CH:7][CH:6]=1)(=[O:3])=[O:4]

Participants

6

Reactant 1

HCID 57550073HCID 57550073, compound

Product 1

HCID 57468384HCID 57468384, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of 4-(2-methylprop-1-enyl)phenyl 4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (30 mg, 0.057 mmol) and palladium on carbon (10 wt. %, wet) (20 mg, 0.188 mmol, Aldrich) in MeOH (4.0 mL) and DMF (0.5 mL) was placed under hydrogen (balloon) for 2 hrs and additional palladium on carbon (20 mg) was added. The resulting mixture was continuously stirred under hydrogen (balloon) for 1.5 hrs, diluted with CH2Cl2, filtrated through a pad of CELITE® 545 filter aid and concentrated in vacuo. The residue was purified by preparative HPLC (C18 column; 30-100% methanol in water containing 0.05% trifluoroacetic acid) to give Example 144 (21.4 mg, yellow solid, 71%) upon lyophilization. 1H NMR (500 MHz, CDCl3) 8.10 (d, J=8.25 Hz, 2 H), 7.61 (d, J=8.25 Hz, 2 H), 7.38 (d, J=7.70 Hz, 1 H), 7.14 (d, J=8.80 Hz, 2 H), 7.00 (d, J=8.25 Hz, 2 H), 6.56 (d, J=2.20 Hz, 1 H), 6.33 (dd, J=7.42, 2.47 Hz, 1 H), 4.62-4.74 (m, 1 H), 3.89-4.04 (m, 1 H), 3.85 (app brs, 1 H), 3.85 (app brs, 1 H), 3.57 (app brs, 1 H), 3.12 (s, 3 H), 2.46 (d, J=7.15 Hz, 2 H), 2.13 (app brs, 2 H), 1.89-1.98 (m, 2 H), 1.80-1.89 (m, 1 H), 0.90 (d, J=6.60 Hz, 6 H). MS (ESI) 525 (M+H).

Workup

  1. filtrationfiltrated through a pad of CELITE® 545
  2. filtrationfilter aid
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by preparative HPLC (C18 column; 30-100% methanol in water containing 0.05% trifluoroacetic acid)
  5. customto give Example 144 (21.4 mg, yellow solid, 71%) upon lyophilization

Sources & evidence

ORD record
ord-bf34deddb6e147b796e8f208aa865284
Source dataset
uspto-grants-2013_08
Patent number
US08513424B2

Reaction notes

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