Methanol → 3-Bromo-n-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamide

HRID 433294

반응식

HRID 433294 반응식
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:18]2[C:26](=[O:27])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][C:24]=3[NH2:28])[C:19]2=[O:29])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[Br:30][CH:31](C)[C:32](Cl)=O.[CH3:36][OH:37]>CCOCC>[Br:30][CH2:31][CH2:32][C:36]([NH:28][C:24]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:25]=1[C:26](=[O:27])[N:18]([CH:12]([C:6]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1)[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[C:19]2=[O:29])=[O:37]

참가 물질

5

반응물 3

HCID 887MethanolHCID 979802-Bromopropanoyl chlorideHCID 98449131H-Isoindole-1,3(2H)-dione, 4-amino-2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-

생성물 1

HCID 187583873-Bromo-n-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamide수율 80%

시약·촉매·용매 1

HCID 3283Diethyl Ether용매

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온도
100 °C

실험 절차

A mixture of 2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-4-aminoisoindoline-1,3-dione (0.80 g, 1.9 mmol) and 2-bromopropionyl chloride (0.8 mL, 7.9 mmol) was heated at 100° C. for 30 min. The mixture was cooled to room temperature. Methanol (10 mL) was added to the mixture. The solvent was removed in vacuo to give an oil. The oil was stirred in ether (10 mL) for 1 day. The resulting suspension was filtered and the solid washed with ether to give 3-bromo-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamide as a yellow solid (0.84 g, 80% yield). A portion of the isolated bromide (620 mg, 1.2 mmol) and dimethylamine (2 mL, 2M in methanol, 4 mmol) was stirred at room temperature for 3 h. The resulting suspension was filtered and washed with methanol to yield the crude product as a yellow solid. The solid was purified by column chromatography to give 3-(dimethylamino)-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamide as a white solid (180 mg, 30% yield): mp, 163-165° C.; 1H NMR (CDCl3) δ1.47 (t, J=6.9 Hz, 3H, CH3), 2.38 (s, 6H, CH3), 2.59 (t, J=5.7 Hz, 2H, CH2), 2.70 (t, J=5.9 Hz, 2H, CH2), 2.82 (s, 3H, CH3), 3.78-3.85 (m, 1H, CHH), 3.86 (s, 3H, CH3), 4.10 (q, J=7.0 Hz, 2H, CH2), 4.49 (dd, J=9.8, 14.6 Hz, 1H, CHH), 5.86 (dd, J=4.9, 9.7 Hz, 1H, NCH), 6.82-6.85 (m, 1H, Ar), 7.10-7.13 (m, 2H, Ar), 7.48 (d, J=7.2 Hz, 1H, Ar), 7.63 (t, J=7.5 Hz, 1H, Ar), 8.82 (d, J=8.4 Hz, 1H, Ar), 11.36 (s, 1H, NH); 13C NMR (CDCl3) δ14.62, 34.85, 41.49, 44.65, 48.74, 54.31, 55.01, 55.88, 64.44, 111.43, 112.52, 115.99, 117.93, 120.39, 120.08, 129.52, 131.42, 135.59, 137.33, 148.55, 149.67, 168.00, 168.16, 171.86; Anal Calcd for C25H31N3O7S: C, 58.01; H, 6.04; N, 8.12. Found: C, 57.75; H, 5.86; N, 7.91.

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. customThe solvent was removed in vacuo
  3. customto give an oil
  4. filtrationThe resulting suspension was filtered
  5. washthe solid washed with ether

출처 및 근거

ORD 기록
ord-c9d92fd9af7640c0b63cf40ead1e791f
출처 데이터셋
uspto-grants-2003_12
특허 번호
US06667316B1

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