Methyl iodide → (1R,2S,7R,8S)-N-{3-[6-hydroxy-3-(3-methyl-butyl)-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-N-methyl-methanesulfonamide

HRID 548326노트

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HRID 548326 반응식
[OH:1][C:2]1[C@H:11]2[C@H:6]([C@H:7]3[CH2:12][C@@H:10]2[CH2:9][CH2:8]3)[N:5]([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C:4](=[O:18])[C:3]=1[C:19]1[NH:24][C:23]2[CH:25]=[CH:26][C:27]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])=[CH:28][C:22]=2[S:21](=[O:35])(=[O:34])[N:20]=1.[C:36](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O>[OH:1][C:2]1[C@H:11]2[C@H:6]([C@H:7]3[CH2:12][C@@H:10]2[CH2:9][CH2:8]3)[N:5]([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C:4](=[O:18])[C:3]=1[C:19]1[NH:24][C:23]2[CH:25]=[CH:26][C:27]([N:29]([CH3:36])[S:30]([CH3:33])(=[O:32])=[O:31])=[CH:28][C:22]=2[S:21](=[O:35])(=[O:34])[N:20]=1

참가 물질

5

반응물 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 135976563(1R,2S,7R,8S)-N-{3-[6-hydroxy-3-(3-methyl-butyl)-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide

생성물 1

HCID 136402454(1R,2S,7R,8S)-N-{3-[6-hydroxy-3-(3-methyl-butyl)-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-N-methyl-methanesulfonamide수율 56.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
25 °C

실험 절차

(1R,2S,7R,8S)-N-{3-[6-Hydroxy-3-(3-methyl-butyl)-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (prepared as described in Example 22, 90 mg, 0.172 mmol) was dissolved in anhydrous N,N-dimethylformamide (2 mL). Potassium carbonate (0.04 g, 0.344 mmol) was added followed by iodomethane (0.027 g, 0.189 mmol). The mixture was stirred at 25° C. for 5 h. The reaction mixture was extracted with ethyl acetate (2×100 mL) and water (100 mL). The organic layer was washed with saturated aqueous brine solution (50 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to afford the crude product, which was purified by flash column chromatography (Teledyne Isco RediSep column; 40% ethyl acetate in hexanes) to afford the desired product, (1R,2S,7R,8S)-N-{3-[6-hydroxy-3-(3-methyl-butyl)-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-N-methyl-methanesulfonamide (0.052 g, 0.097 mmol, 56.4%), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 0.92 (6H, d, J=6.4 Hz), 1.21-1.26 (1H, m), 1.28-1.33 (1H, m), 1.39-1.63 (7H, m), 2.54 (1H, bs), 2.63-2.67 (1H, m), 3.00 (3H, s), 3.06-3.17 (1H, m), 3.29 (3H, s), 3.63-3.72 (2H, m), 7.62 (1H, d, J=8.5 Hz), 7.70-7.73 (1H, m), 7.85 (1H, s). LC-MS (ESI) calcd for C24H32N4O6S2 536.18, found 537.6.6 [M+H+].

후처리

  1. extractionThe reaction mixture was extracted with ethyl acetate (2×100 mL) and water (100 mL)
  2. washThe organic layer was washed with saturated aqueous brine solution (50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customto afford the crude product, which
  7. customwas purified by flash column chromatography (Teledyne Isco RediSep column; 40% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-5011335fb90f4165bdd05400a8ecdd1b
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07939524B2

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