Water → 5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinone

HRID 1271135

反応式

HRID 1271135 の反応式
Cl[C:2]1[C:3](=[O:15])[N:4]([CH:9]([CH2:12][O:13][CH3:14])[CH2:10][CH3:11])[CH:5]=[C:6]([Cl:8])[N:7]=1.Cl.[Cl:17][C:18]1[CH:19]=[C:20]([O:27][CH3:28])[CH:21]=[C:22]2[C:26]=1[NH:25][CH2:24][CH2:23]2.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O>O1CCCC1>[Cl:8][C:6]1[N:7]=[C:2]([N:25]2[C:26]3[C:22](=[CH:21][C:20]([O:27][CH3:28])=[CH:19][C:18]=3[Cl:17])[CH2:23][CH2:24]2)[C:3](=[O:15])[N:4]([CH:9]([CH2:12][O:13][CH3:14])[CH2:10][CH3:11])[CH:5]=1

参加物

6

反応物 4

HCID 962WaterHCID 2724254Sodium bis(trimethylsilyl)amideHCID 184527983,5-dichloro-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinoneHCID 184528197-Chloro-5-methoxyindoline hydrochloride

生成物 1

HCID 102008575-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinone収率 20.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To 3,5-dichloro-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinone (1.0 g), prepared as described in Scheme 4, and 7-chloro-5-methoxyindoline hydrochloride (0.92 g), prepared as described in U.S. Pat. No. 6,245,769, stirring in anhydrous tetrahydrofuran (25 mL, 0° C.) was added sodium bis(trimethylsilyl)amide (1.0 M in THF, 11.9 mL, dropwise). The reaction mixture was allowed to come to ambient temperature and stirred 18 hours. Water was added, and the mixture was extracted with three portions of ethyl acetate. The combined ethyl acetate extracts were washed with brine, dried over MgSO4, and concentrated. The crude product was chromatographed on silica gel using ethyl acetate/hexane (1:4) as eluent to afford the title compound (329 mg). mp 131–133° C. 1H-NMR (CDCl3) δ: 0.93 (3H, t, J=7.3 Hz), 1.83 (2H, m), 3.09 (2H, t, J=7.6 Hz), 3.35 (3H, s), 3.56 (1H, dd), 3.67 (1H, dd), 3.78 (3H, s), 4.34 (2H, t, J=7.7 Hz), 4.94 (1H, m), 6.74 (2H, s), 6.99 (1H, s). MS (APCI+) m/z 398 (M+H)+.

後処理

  1. customprepared
  2. customto come to ambient temperature
  3. extractionthe mixture was extracted with three portions of ethyl acetate
  4. washThe combined ethyl acetate extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was chromatographed on silica gel

出典と根拠

ORDレコード
ord-2ddba86792e14110a9b385443dad8f4d
出典データセット
uspto-grants-2007_04
特許番号
US07205306B2

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