Sodium Iodide → 7-(4-(4-(2-methoxyphenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one

HRID 1750097Notes

Reaction equation

HRID 1750097 reaction equation
CS(O[CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:20]=[CH:19][C:18]2[CH2:17][CH2:16][C:15](=[O:21])[NH:14][C:13]=2[N:12]=1)(=O)=O.[Na+].[I-].Cl.[CH3:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[N:33]1[CH2:39][CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.C([O-])([O-])=O.[K+].[K+]>CC#N.O>[CH3:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[N:33]1[CH2:39][CH2:38][CH2:37][N:36]([CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]2[N:12]=[C:13]3[C:18]([CH2:17][CH2:16][C:15](=[O:21])[NH:14]3)=[CH:19][CH:20]=2)[CH2:35][CH2:34]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 190955641-(2-methoxyphenyl)-1,4-diazepane HClHCID 870843174-(7-Oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yloxy)butyl methanesulfonate

Product 1

HCID 565988777-(4-(4-(2-methoxyphenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-oneYield 20%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 12 (150 mg, 0.48 mmol) and NaI (141 mg, 0.94 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 29 (114 mg, 0.47 mmol) and anhydrous K2CO3 (260 mg, 1.88 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred overnight. The reaction solution was diluted with water and extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2SO4, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with DCM/MeOH=30:1) to give 7-(4-(4-(2-methoxyphenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one (compound 11) (40 mg, 17%). HPLC: 95%, RT 2.400 min. MS (EST) m/z 422.2 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 30 min
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux
  5. extractionextracted with EtOAc
  6. washThe combined EtOAc layers were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated in vacuo
  9. custompurified by flash chromatography on silica gel column (elution with DCM/MeOH=30:1)

Sources & evidence

ORD record
ord-ca8e48bbe20a41c0b30ee04f412c87d9
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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