Sodium Iodide → HCID 54720512, compound

HRID 1817354Notes

Reaction equation

HRID 1817354 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16]([N:18]([CH3:20])[CH3:19])=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].C[O-].[Mg+2].C[O-].Br[CH2:34][CH2:35]Cl.[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1.[I-].[Na+]>CO.CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]([CH2:39][CH2:38][N:37]3[CH2:35][CH2:34][CH2:40][CH2:41]3)[C:12]=2[C:16]([N:18]([CH3:20])[CH3:19])=[O:17])[C:7]1=[O:23]

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 78491-Bromo-2-ChloroethaneHCID 31268PyrrolidineHCID 164537Methanol, magnesium salt (2:1)HCID 178484497HCID 178484497, compound

Product 1

HCID 54720512HCID 54720512, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide (0.075 g, 0.19 mmol; Example 13, step 5) and magnesium methoxide in methanol (0.06 mL, 6-10% methanol solution available from Aldrich) in DMSO (2 mL) was heated at 60° C. for 30 minutes. Methanol was exhaustively removed under vacuum over 45 minutes. The residual DMSO solution was treated with 1-bromo-2-chloroethane (0.136 g, 0.95 mmol) and stirred at 60° C. under an atmosphere of nitrogen overnight. The product mixture was treated with pyrrolidine (0.27 g, 3.8 mmol) and sodium iodide (0.14 g, 0.95 mmol) and heated at 60° C. overnight. The reaction was partitioned between methylene chloride and aqueous sodium bisulfate. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to preparative HPLC purification on C-18 reverse stationary phase column eluting with a gradient of water—acetonitrile in the presence of 0.1% trifluoroacetic acid. Collection and lyophilization of appropriate fractions provided the titled compound.

Workup

  1. customMethanol was exhaustively removed under vacuum over 45 minutes
  2. temperatureheated at 60° C. overnight
  3. customThe reaction was partitioned between methylene chloride and aqueous sodium bisulfate
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was subjected to preparative HPLC purification on C-18 reverse stationary phase column
  9. washeluting with a gradient of water—acetonitrile in the presence of 0.1% trifluoroacetic acid
  10. customCollection and lyophilization of appropriate fractions

Sources & evidence

ORD record
ord-af8a4ac5ee77452ab1e5aaf8f9af033e
Source dataset
uspto-grants-2009_10
Patent number
US07598264B2

Reaction notes

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