Tetrahydrofuran → 2-((1H-indol-4-yl)methyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

HRID 41543Notes

Reaction equation

HRID 41543 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[CH:38]=[CH:37][CH:36]=[C:35]2[C:31]=1[CH:32]=[CH:33][N:34]2S(C1C=CC(C)=CC=1)(=O)=O>[NH4+].[Cl-]>[NH:34]1[C:35]2[C:31](=[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:38]=[CH:37][CH:36]=2)[CH:32]=[CH:33]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 13044879HCID 13044879, compoundHCID 672517459-(Quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

Product 1

HCID 532591122-((1H-indol-4-yl)methyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-oneYield 55.3%

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 9-quinoxalin-2-yl-2,9-diaza-spiro[5.5]undecan-1-one (100 mg, 0.34 mmol) in THF (5 ml) sodium hydride 95% (18 mg, 0.74 mmol) was added and the mixture was stirred for 10 min at rt. Then 4-bromomethyl-1-(toluene-4-sulfonyl)-1H-indole (147 mg, 0.4 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 4:6) to yield 80 mg (55%) of the title compound. [1H NMR (DMSO, 600 MHz) δ 11.14 (br.s, 1H), 8.84 (s, 1H), 7.81 (d, 1H, J=8.28 Hz), 7.63-7.52 (m, 2H), 7.44-7.34 (m, 2H), 7.34-7.25 (m, 2H), 7.03 (t, 1H), 6.82 (d, 1H, J=7.06 Hz), 6.43 (br.s., 1H), 4.76 (s, 2H), 4.35-4.25 (m, 2H), 3.48-3.38 (2H, m), 3.13 (t, 2H), 2.21-2.04 (m, 2H), 1.91-1.80 (m, 2H), 1.77-1.65 (m, 2H), 1.62-1.52 (m, 2H), LCMS RtE=2.70 min, [M+H]+=426.4].

Workup

  1. temperaturethe reaction mixture was heated at 50° C. over 18 h
  2. extractionthe reaction mixture was extracted with methylene chloride
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting crude product was purified by flash chromatography (EtOAc/hexane 4:6)

Sources & evidence

ORD record
ord-1ea18d2ac6794360b7000ebcecf3c852
Source dataset
uspto-grants-2013_09
Patent number
US08530648B2

Reaction notes

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