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 386665Notes

Reaction equation

HRID 386665 reaction equation
[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]

Participants

6

Reactant 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

Product 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}-amideYield 30.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 313Hydrochloric AcidSolventHCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-bda90dd1e2824ccda00ba24c5ce87652
Source dataset
uspto-grants-2013_02
Patent number
US08372865B2

Reaction notes

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