Tetrahydrofuran → 2-((2,3-Dihydrobenzo[b][1,4]dioxin-5-yl)methyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

HRID 41544Notes

Reaction equation

HRID 41544 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.C1COCC1.Br[CH2:29][C:30]1[C:39]2[O:38][CH2:37][CH2:36][O:35][C:34]=2[CH:33]=[CH:32][CH:31]=1>[NH4+].[Cl-]>[O:35]1[CH2:36][CH2:37][O:38][C:39]2[C:30]([CH2:29][N:18]3[CH2:17][CH2:16][CH2:15][C:14]4([CH2:21][CH2:22][N:11]([C:2]5[CH:3]=[N:4][C:5]6[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=6)[N:1]=5)[CH2:12][CH2:13]4)[C:19]3=[O:20])=[CH:31][CH:32]=[CH:33][C:34]1=2

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 153808895-(Bromomethyl)-2,3-dihydro-1,4-benzodioxineHCID 672517459-(Quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

Product 1

HCID 532591132-((2,3-Dihydrobenzo[b][1,4]dioxin-5-yl)methyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-oneYield 79.9%

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 9-quinoxalin-2-yl-2,9-diaza-spiro[5.5]undecan-1-one (50 mg, 0.169 mmol) in THF (2 ml) sodium hydride 95% (6.07 mg, 0.253 mmol) was added and the mixture was stirred for 20 min. Then 5-bromomethyl-2,3-dihydro-benzo[1,4]dioxin (77 mg, 0.337 mmol) was added and the reaction mixture was heated at 50° C. over 18 h. Saturated aqueous NH4Cl solution (50 ml) was added and the reaction mixture was extracted with methylene chloride. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting crude product was purified by flash chromatography (EtOAc/hexane 70:30) to yield 60 mg (79%) of the title compound. [1H NMR (600 MHz, DMSO-d6) δ 1.54-1.66 (2H, m) 1.76-1.84 (2H, m) 1.87-1.93 (2H, m) 2.02-2.12 (2H, m) 3.23 (2H, t) 3.39-3.47 (2H, m) 4.20-4.23 (2H, m) 4.24-4.27 (3H, m) 4.27-4.30 (1H, m) 4.41 (2H, s) 6.54 (1H, m) 6.72-6.75 (1H, m) 6.75-6.79 (1H, m) 7.32-7.41 (1H, m) 7.49-7.63 (2H, m) 7.80 (1H, d, J=8.07 Hz), 8.82 (1H, s), LCMS RtD=3.27 min, [M+H]+=445.2].

Workup

  1. extractionthe reaction mixture was extracted with methylene chloride
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting crude product was purified by flash chromatography (EtOAc/hexane 70:30)

Sources & evidence

ORD record
ord-25c1cb6dcce449658c29439c6e9a96ff
Source dataset
uspto-grants-2013_09
Patent number
US08530648B2

Reaction notes

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