Dimethylformamide → 2-(Naphthalen-1-ylmethyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

HRID 41540

Reaction equation

HRID 41540 reaction equation
[O:1]=[C:2]1[C:7]2([CH2:12][CH2:11][N:10]([C:13](OC(C)(C)C)=O)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][NH:3]1.[H-].[Na+].Cl[CH2:23][C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][CH:25]=1.[CH3:34][N:35]([CH:37]=O)C>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:24]1([CH2:23][N:3]2[CH2:4][CH2:5][CH2:6][C:7]3([CH2:8][CH2:9][N:10]([C:13]4[CH:34]=[N:35][C:37]5[C:2](=[CH:7][CH:6]=[CH:5][CH:4]=5)[N:3]=4)[CH2:11][CH2:12]3)[C:2]2=[O:1])[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 68451-ChloromethylnaphthaleneHCID 24758Sodium hydrideHCID 49760149tert-Butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate

Product 1

HCID 532591112-(Naphthalen-1-ylmethyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-oneYield 61%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of tert-butyl 1-Oxo-2,9-diaza-spiro[5.5]undecane-9-carboxylate (400 mg, 1.5 mmol) in DMF (2 ml) was added slowly at rt to a suspension of sodium hydride 95% (54 mg, 2.24 mmol) in THF (6 ml). The reaction mixture was stirred for 20 min at rt. Then a solution of 1-(chloromethyl)naphthalene (0.33 ml, 2.24 mmol) in THF (2 ml) was added dropwise followed by the addition of tetrabutylammonium iodide (55 mg, 0.15 mmol). The mixture was stirred at 45° C. for 18 h. The reaction mixture was quenched with H2O (50 ml) and extracted twice with EtOAc (50 ml). The combined organic layer was dried over Na2SO4, filtered and evaporated. The residue was purified by flash chromatography (hexane/EtOAc 2:1) to yield 377 mg (61%) of the title compound. [1H NMR (DMSO, 400 MHz) δ 8.01 (m, 1H), 7.93 (m, 1H), 7.85 (m, 1H), 7.55-7.42 (m, 3H), 7.30 (m, 1H), 4.95 (s, 2H), 3.72 (m, 2H), 3.15-2.95 (m, 4H), 1.98-1.82 (m, 2H), 1.78-1.62 (m, 4H), 1.48-1.38 (m, 2H), 1.39 (s, 9H)].

Workup

  1. stirringThe mixture was stirred at 45° C. for 18 h
  2. customThe reaction mixture was quenched with H2O (50 ml)
  3. extractionextracted twice with EtOAc (50 ml)
  4. dry with materialThe combined organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash chromatography (hexane/EtOAc 2:1)

Sources & evidence

ORD record
ord-393facae0d6c422b8d21b173d5c6f557
Source dataset
uspto-grants-2013_09
Patent number
US08530648B2

Linked notes

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