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

HRID 41543ノート

反応式

HRID 41543 の反応式
[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

参加物

5

反応物 3

HCID 8028TetrahydrofuranHCID 130448794-bromomethyl-1-(toluene-4-sulfonyl)-1H-indoleHCID 672517459-(Quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

生成物 1

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

試薬・触媒・溶媒 1

HCID 25517Ammonium Chloride溶媒

実験手順

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].

後処理

  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)

出典と根拠

ORDレコード
ord-1ea18d2ac6794360b7000ebcecf3c852
出典データセット
uspto-grants-2013_09
特許番号
US08530648B2

反応ノート

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