1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indazol-6-ylamine → (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indazol-6-yl}-amide

HRID 386665노트

반응식

HRID 386665 반응식
[C:1]([Si:5]([CH3:21])([CH3:20])[O:6][CH2:7][CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([CH3:19])=[C:15]([NH2:18])[CH:16]=2)[CH:11]=[N:10]1)([CH3:4])([CH3:3])[CH3:2].[F:22][C:23]1[CH:28]=[CH:27][C:26]([C@@H:29]2[CH2:34][C:33](=[O:35])[NH:32][CH:31]=[C:30]2[C:36](Cl)=[O:37])=[CH:25][CH:24]=1>N1C=CC=CC=1.CN(C1C=CN=CC=1)C.Cl>[C:1]([Si:5]([CH3:21])([CH3:20])[O:6][CH2:7][CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([CH3:19])=[C:15]([NH:18][C:36]([C:30]3[C@H:29]([C:26]4[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=4)[CH2:34][C:33](=[O:35])[NH:32][CH:31]=3)=[O:37])[CH:16]=2)[CH:11]=[N:10]1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

6

반응물 2

HCID 582002541-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indazol-6-ylamineHCID 59377403(S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid chloride

생성물 1

HCID 59377449(S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indazol-6-yl}-amide수율 30.3%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 313Hydrochloric Acid용매HCID 1049Pyridine용매

반응 조건

온도
90 °C

실험 절차

1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indazol-6-ylamine (89 mg, 0.29 mmol) and (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid chloride (74 mg, 0.29 mmol, prepared as described in Example 1) were dissolved in pyridine (2 ml) together with a crystal of DMAP and sealed in a tube. The mixture was heated to 90° C. with stirring for 18 hours. Upon cooling the mixture was diluted with dilute aqueous HCl solution and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (95:5 dichloromethane/methanol) to give 46 mg (30.3%) of (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indazol-6-yl}-amide as a yellow oil.

후처리

  1. customsealed in a tube
  2. temperatureUpon cooling the mixture
  3. extractionextracted with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (95:5 dichloromethane/methanol)

출처 및 근거

ORD 기록
ord-bda90dd1e2824ccda00ba24c5ce87652
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372865B2

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