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Lithium hexamethyldisilazane → HCID 68006113, compound

HRID 1026599
Notes
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Reaction equation

HRID 1026599 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:25])[N:9]2[CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)=[N:4][CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].Br[CH2:37][CH2:38][O:39][CH2:40][C:41]1[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=1>O.CN1CCCN(C)C1=O.O1CCCC1.CCCCCC>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH:7]([CH2:37][CH2:38][O:39][CH2:40][C:41]3[CH:42]=[CH:43][C:44]([O:47][CH3:48])=[CH:45][CH:46]=3)[C:8](=[O:25])[N:9]2[CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:14][CH2:13]2)=[N:4][CH:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 3

HCID 2733832Lithium hexamethyldisilazaneHCID 117015101-((2-Bromoethoxy)methyl)-4-methoxybenzeneHCID 68006101HCID 68006101, compound

Product 1

HCID 68006113HCID 68006113, compoundYield 29.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent
HCID 8028
Tetrahydrofuran
Solvent
2×
HCID 8058HexaneSolvent
HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

To a tetrahydrofuran solution (2 ml) of tert-butyl 4-(7-chloro-2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)piperidine-1-carboxylate (Reference Example 9-3) (438 mg) was added dropwise at −20° C. a hexane solution (1.0 M, 1.32 ml) of lithium hexamethyldisilazide over 10 minutes. After the reaction solution was stirred for 30 minutes, was added dropwise a tetrahydrofuran solution of 1-(2-bromoethoxymethyl)-4-methoxybenzene (Journal of Medicinal Chemistry, 2007, 50(26), 6580-6595)(324 mg) and 1,3-dimethyltetrahydropyrimidin-2(1H)-one (315 mg). The reaction solution was brought to 0° C. over 30 minutes, and then stirred for 90 minutes. Water was added to the reaction solution, and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford tert-butyl 4-[7-chloro-3-{2-[(4-methoxybenzyl)oxy]ethyl}-2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl]piperidine-1-carboxylate (189 mg).

Workup

  1. waitThe reaction solution was brought to 0° C. over 30 minutes
  2. stirringstirred for 90 minutes
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-173537e59b1e46e7b348d6ba85757c0f
Source dataset
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08729095B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes