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

HRID 41543노트

반응식

HRID 41543 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 25517Ammonium Chloride용매

실험 절차

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].

후처리

  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)

출처 및 근거

ORD 기록
ord-1ea18d2ac6794360b7000ebcecf3c852
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530648B2

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