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

반응식

HRID 1035850 반응식
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]

참가 물질

8

반응물 5

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

생성물 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-one수율 83.3%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-cf4dee6a5deb49ba9d5f086220bd613f
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546401B2

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