Sodium hydride → 2-(3-(Pyridin-3-yl)benzyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

HRID 41545Notes

Reaction equation

HRID 41545 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[CH:3][C:2]=1[N:11]1[CH2:22][CH2:21][C:14]2([C:19](=[O:20])[NH:18][CH2:17][CH2:16][CH2:15]2)[CH2:13][CH2:12]1.[H-].[Na+].Cl[CH2:26][C:27]1[CH:28]=[C:29]([C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)[CH:30]=[CH:31][CH:32]=1>C1COCC1>[N:35]1[CH:36]=[CH:37][CH:38]=[C:33]([C:29]2[CH:28]=[C:27]([CH:32]=[CH:31][CH:30]=2)[CH2:26][N:18]2[CH2:17][CH2:16][CH2:15][C:14]3([CH2:21][CH2:22][N:11]([C:2]4[CH:3]=[N:4][C:5]5[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=5)[N:1]=4)[CH2:12][CH2:13]3)[C:19]2=[O:20])[CH:34]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 190793993-(3-Chloromethyl-phenyl)-pyridineHCID 672517459-(Quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

Product 1

HCID 532592782-(3-(Pyridin-3-yl)benzyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-oneYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one (0.035 g, 0.12 mmol) in dry THF (4.0 mL), NaH (0.014 g, 0.36 mmol) was added at rt and the mixture was stirred for 10 min. 3-(3-Chloromethyl-phenyl)-pyridine (0.05 g, 0.24 mmol) was then added and the reaction mixture was heated to 60° C. for 6 h. The mixture was quenched with 1 ml saturated aqueous NH4Cl solution, diluted with 50 ml water and the resulting mixture was extracted with ethyl acetate (100 mL). The organic layer was washed with water and brine. The organic layer was dried over Na2SO4, filtered and concentrated to obtain the crude product. Preparative HPLC purification furnished the title compound as a pale yellow sticky solid (0.025 g, 46%). [1H-NMR (CDCl3, 300 MHz): δ 8.84-8.81 (m, 1H), 8.66-8.58 (m, 2H), 7.92-7.81 (m, 2H), 7.72-7.65 (m, 1H), 7.35-7.61 (m, 6H), 4.68 (s, 2H), 4.31-4.20 (m, 2H), 3.70-3.55 (m, 2H), 3.31 (t, 2H), 2.43-2.29 (m, 2H), 1.96-1.82 (m, 4H), 1.75-1.63 (dt, 2H); HPLC RtA=4.635 min (96%); LCMS RtC=0.395, [M+H]+=464.0].

Workup

  1. customThe mixture was quenched with 1 ml saturated aqueous NH4Cl solution
  2. additiondiluted with 50 ml water
  3. extractionthe resulting mixture was extracted with ethyl acetate (100 mL)
  4. washThe organic layer was washed with water and brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto obtain the crude product
  9. customPreparative HPLC purification

Sources & evidence

ORD record
ord-83a33ac8b4e64bb0b31f91bf4324c79f
Source dataset
uspto-grants-2013_09
Patent number
US08530648B2

Reaction notes

Loading…