1-Iodo-3-methylbutane → 6-(3-Chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5-(3-methyl-butyl)-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester

HRID 2047704

Reaction equation

HRID 2047704 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[NH:11][CH:10]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[C:17]([Cl:22])[CH:16]=3)[CH2:9][C:8]([CH2:24][CH3:25])([CH3:23])[C:7]=2[N:6]=1)=[O:4].[H-].[Na+].I[CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32]>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[N:11]([CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32])[CH:10]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[C:17]([Cl:22])[CH:16]=3)[CH2:9][C:8]([CH2:24][CH3:25])([CH3:23])[C:7]=2[N:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 109241-Iodo-3-methylbutaneHCID 24758Sodium hydrideHCID 66587522HCID 66587522, compound

Product 1

HCID 665877056-(3-Chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5-(3-methyl-butyl)-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl esterYield 73.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of 6-(3-chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester (200 mg, 0.5 mmol) in N,N-dimethylformamide (5 mL) was added a 60% dispersion of sodium hydride in mineral oil (44 mg, 1.1 mmol) portionwise. The mixture was stirred at 0° C. for 30 min and then 1-iodo-3-methyl-butane (327 mg, 1.6 mmol) was added to above mixture dropwise at 0° C. The mixture was stirred at 0° C. for 3 hours and then extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The yellowish residue was purified by ISCO combi-flash chromatography (gradient elution, 0-5% ethyl acetate/hexane) to afford 6-(3-chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5-(3-methyl-butyl)-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester (160 mg, 67.5%) as a yellow oil. MS (ESI+) [(M+H)+] 433.1.

Workup

  1. stirringThe mixture was stirred at 0° C. for 3 hours
  2. extractionextracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe yellowish residue was purified by ISCO combi-flash chromatography (gradient elution, 0-5% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-94d32a24d5124111b84cf2d5c19ac397
Source dataset
uspto-grants-2013_11
Patent number
US08592594B2

Linked notes

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