Methyl iodide → 1'-{[(2S)-1-methyl-5-oxopyrrolidin-2-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1H)-one

HRID 1965697노트

반응식

HRID 1965697 반응식
[O:1]=[C:2]1[NH:6][C@H:5]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3([CH2:20][O:19][C:18]4[CH:21]=[C:22]5[C:26](=[CH:27][C:17]3=4)[CH2:25][CH2:24][O:23]5)[C:9]2=[O:28])[CH2:4][CH2:3]1.[H-].[Na+].I[CH3:32]>CN(C)C=O>[CH3:32][N:6]1[C:2](=[O:1])[CH2:3][CH2:4][C@H:5]1[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]2([CH2:20][O:19][C:18]3[CH:21]=[C:22]4[C:26](=[CH:27][C:17]2=3)[CH2:25][CH2:24][O:23]4)[C:9]1=[O:28]

참가 물질

5

반응물 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 593520751'-{[(2S)-5-oxopyrrolidin-2-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1'H)-one

생성물 1

HCID 593521491'-{[(2S)-1-methyl-5-oxopyrrolidin-2-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1H)-one수율 62%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a stirred solution of 1′-{[(2S)-5-oxopyrrolidin-2-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.235 g, 0.623 mmol) in dry N,N-dimethylformamide (10 mL) was added sodium hydride (60% in mineral oil, 0.04 g, 1.04 mmol) at ambient temperature. The mixture was stirred for 15 min, and iodomethane (0.28 g, 2.0 mmol) was added in one portion. The reaction mixture was stirred at ambient temperature for 1 h, and concentrated to dryness. The residue was purified by flash chromatography (hexanes/ethyl acetate; gradient 0% to 30%) to afford 1′-{[(2S)-1-methyl-5-oxopyrrolidin-2-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1H)-one (0.15 g, 62%) as colorless solid: mp 72-76° C.; 1H NMR (300 MHz, CDCl3) δ7.33 (dd, J=7.5, 7.5 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.09 (dd, J=7.5, 7.5 Hz, 1H), 6.91 (d, J=7.5 Hz, 1H), 6.46-6.38 (m, 2H), 4.77 (ABq, 2H), 4.53 (t, J=8.6 Hz, 2H), 4.03-3.75 (m, 3H), 3.11-2.83 (m, 5H), 2.61-2.42 (m, 1H), 2.42-2.27 (m, 1H), 2.26-2.07 (m, 1H), 2.03-1.84 (m, 1H); 13C NMR (75 MHz, CDCl3) δ178.4, 178.4, 175.1, 175.0, 161.8, 161.3, 161.2, 142.1, 141.9, 132.5, 132.4, 128.9 (2C), 124.3, 124.2, 123.7 (2C), 120.0, 119.9, 119.7, 119.6, 118.6, 118.5, 108.0, 93.2, 80.5, 72.3, 58.1, 58.0, 57.5 (2C), 43.0, 42.9, 29.3, 29.2, 28.9, 28.7 (2C), 22.6 (2C); MS (ES+) m/z 391.1 (M+1).

후처리

  1. stirringThe reaction mixture was stirred at ambient temperature for 1 h
  2. concentrationconcentrated to dryness
  3. customThe residue was purified by flash chromatography (hexanes/ethyl acetate; gradient 0% to 30%)

출처 및 근거

ORD 기록
ord-f1a5738015ac49018366005f77968788
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415370B2

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