Diazomethane → HCID 54681837, compound

HRID 1817371Notes

Reaction equation

HRID 1817371 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([O:20]C)[C:10](=[O:19])[N:11]([CH3:18])[C:12]=2[CH2:16][CH3:17])[C:7]1=[O:22].[N+](=[CH2:29])=[N-]>C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:20])[C:10](=[O:19])[N:11]([CH3:18])[C:12]=2[CH:16]2[CH2:29][CH2:17]2)[C:7]1=[O:22]

Participants

5

Reactant 2

HCID 9550DiazomethaneHCID 69061871HCID 69061871, compound

Product 1

HCID 54681837HCID 54681837, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolvent2×

Procedure

To a cold (0° C.) solution of 2-(3-chloro-4-fluorobenzyl)-5-vinyl-8-methoxy-6-methyl-2,3,4,6-tetrahydro-2,6-naphthyridine-1,7-dione (0.12 g, 0.32 mmol; Example 83, step 2) in diethyl ether (5 mL), a solution of diazomethane (˜3 mmol) in diethyl ether was added. Catalytic amount of palladium (II) acetate was added and the mixture was stirred at the same temperature for 30 minutes. The product mixture was filtered and concentrated under vacuum. The residue was subjected to preparative reverse phase HPLC purification. Collection and lyophilization of appropriate fractions provide the cyclopropanation intermediate. Following the demethylation procedure described in Example 83, step 3, the above intermediate was converted to the titled compound.

Workup

  1. filtrationThe product mixture was filtered
  2. concentrationconcentrated under vacuum
  3. customThe residue was subjected to preparative reverse phase HPLC purification
  4. customCollection and lyophilization of appropriate fractions
  5. customprovide the cyclopropanation intermediate

Sources & evidence

ORD record
ord-e3eb488b7f3949e681f06e6d95a6abec
Source dataset
uspto-grants-2009_10
Patent number
US07598264B2

Reaction notes

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