Water → N-[6-(3-Azabicyclo[3.2.0]hept-3-yl)pyridin-3-yl]-5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamide

HRID 2041954Notes

Reaction equation

HRID 2041954 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[N:12]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=3)[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([F:20])=[CH:15][CH:14]=3)=[O:10])=[CH:4][CH:3]=1.[CH:29]12[CH2:35][CH2:34][CH:33]1[CH2:32][NH:31][CH2:30]2.[OH-].[K+].O>CN1CCCC1=O>[CH:29]12[CH2:35][CH2:34][CH:33]1[CH2:32][N:31]([C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]([C:11]3[N:12]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=4)[C:13]4[C:18]([CH:19]=3)=[CH:17][C:16]([F:20])=[CH:15][CH:14]=4)=[O:10])=[CH:4][CH:3]=1)[CH2:30]2

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 219625873-Azabicyclo[3.2.0]heptaneHCID 86631224N-[6-chloropyridin-3-yl]-5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamide

Product 1

HCID 57431498N-[6-(3-Azabicyclo[3.2.0]hept-3-yl)pyridin-3-yl]-5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamideYield 15.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 0.2 g (0.5 mmol) of N-[6-chloropyridin-3-yl]-5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamide, prepared in step 3.1, of 0.0806 g (0.6 mmol) of 3-azabicyclo[3.2.0]heptane (J. Med. Chem. 1967, 10(4), 621) and of 0.0564 g (1.01 mmol) of potassium hydroxide in 0.5 ml of N-methylpyrrolidinone is heated for 90 minutes in a microwave oven regulated at 150° C. under 150 watts. The reaction mixture is subsequently poured into 20 ml of water. The mixture is extracted with three times 30 ml of ethyl acetate. The combined organic phases are washed with 30 ml of water, dried over sodium sulfate, and then concentrated under reduced pressure. The resulting solid is subsequently purified by silica column chromatography, elution being carried out with a mixture of n-heptane and ethyl acetate. 35 mg of the expected product are thus isolated.

Workup

  1. temperatureis heated for 90 minutes in a microwave oven
  2. customregulated at 150° C. under 150 watts
  3. extractionThe mixture is extracted with three times 30 ml of ethyl acetate
  4. washThe combined organic phases are washed with 30 ml of water
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting solid is subsequently purified by silica column chromatography, elution
  8. additionbeing carried out with a mixture of n-heptane and ethyl acetate

Sources & evidence

ORD record
ord-57616386189240f982b5e5482da4bcb7
Source dataset
uspto-grants-2013_11
Patent number
US08586573B2

Reaction notes

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