Sodium Hydroxide → 5-Chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-3-{2-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-2-oxo-ethyl}-1,3-dihydroindol-2-one

HRID 1035850

反応式

HRID 1035850 の反応式
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:37][N:38]1[CH2:43][CH2:42][CH:41]([N:44]2[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]2)[CH2:40][CH2:39]1.[Cl:50][C:51]1[CH:52]=[C:53]2[C:57](=[CH:58][C:59]=1[F:60])[NH:56][C:55](=[O:61])[C:54]2([CH2:71][C:72](O)=[O:73])[C:62]1[C:63]([O:68][CH2:69][CH3:70])=[N:64][CH:65]=[CH:66][CH:67]=1.[OH-].[Na+]>ClCCl.C(OCC)(=O)C>[Cl:50][C:51]1[CH:52]=[C:53]2[C:57](=[CH:58][C:59]=1[F:60])[NH:56][C:55](=[O:61])[C:54]2([C:62]1[C:63]([O:68][CH2:69][CH3:70])=[N:64][CH:65]=[CH:66][CH:67]=1)[CH2:71][C:72]([N:47]1[CH2:48][CH2:49][N:44]([CH:41]2[CH2:40][CH2:39][N:38]([CH3:37])[CH2:43][CH2:42]2)[CH2:45][CH2:46]1)=[O:73]

参加物

8

反応物 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 5663241-(1-Methyl-4-piperidinyl)piperazineHCID 67087607HCID 67087607、化合物

生成物 1

HCID 670875065-Chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-3-{2-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-2-oxo-ethyl}-1,3-dihydroindol-2-one収率 83.3%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

200 mg (0.45 mmol) of BOP, 1.07 ml (6.17 mmol) of diisopropylethylamine and then 79 mg (0.43 mmol) of 1-(1-methylpiperidin-4-yl)piperazine were added to a solution of 150 mg (0.41 mmol) of [5-chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indol-3-yl]acetic acid in 2 ml of dichloromethane. The reaction mixture was stirred at room temperature overnight. 6 ml of a 2-molar NaOH were added to the reaction solution, and it was stirred at room temperature for 15 minutes. The reaction mixture was diluted with ethyl acetate. The phases were separated and the aqueous phase was extracted with ethyl acetate (1×). The combined organic phase was again washed with water (1×) and saturated sodium chloride solution (1×), dried over magnesium sulfate and filtered, and the solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 2 to 50% methanol in dichloromethane). 181 mg of the title compound were obtained as a white solid.

後処理

  1. stirringwas stirred at room temperature for 15 minutes
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate (1×)
  4. washThe combined organic phase was again washed with water (1×) and saturated sodium chloride solution (1×)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent was evaporated in vacuo
  8. customThe residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 2 to 50% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-cf4dee6a5deb49ba9d5f086220bd613f
出典データセット
uspto-grants-2013_10
特許番号
US08546401B2

関連ノート

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