Triethylamine → HCID 67048783, compound

HRID 2368452Notes

Reaction equation

HRID 2368452 reaction equation
ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:23]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29](=[O:34])[C:28]2([CH2:44][C:45]([OH:47])=O)[C:35]1[C:36]([O:41][CH2:42][CH3:43])=[N:37][CH:38]=[CH:39][CH:40]=1)#[N:24].[CH3:48][N:49]1[CH2:54][CH2:53][N:52]([CH:55]2[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]2)[CH2:51][CH2:50]1.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C.O.ClCCl.CO>[CH2:42]([O:41][C:36]1[C:35]([C:28]2([CH2:44][C:45]([N:58]3[CH2:57][CH2:56][CH:55]([N:52]4[CH2:51][CH2:50][N:49]([CH3:48])[CH2:54][CH2:53]4)[CH2:60][CH2:59]3)=[O:47])[C:27]3[C:31](=[CH:32][CH:33]=[C:25]([C:23]#[N:24])[CH:26]=3)[NH:30][C:29]2=[O:34])=[CH:40][CH:39]=[CH:38][N:37]=1)[CH3:43]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 7957071-Methyl-4-(piperidin-4-yl)piperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67048599HCID 67048599, compound

Product 1

HCID 67048783HCID 67048783, compoundYield 66.9%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

200 mg (1.48 mmol) of 1-hydroxybenzotriazole and 284 mg (1.48 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride were added to a solution of 907 mg (1.48 mmol) of [5-cyano-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]acetic acid from example 1.6 in 10 ml of dimethylformamide. The mixture was stirred for 15 minutes and then 285 mg (1.56 mmol) of 1-methyl-4-piperidin-4-ylpiperazine and 1.03 ml (7.41 mmol) of triethylamine were added. The reaction mixture was stirred at room temperature overnight. The reaction was checked by TLC (silica gel, dichloromethane/methanol 15:5). The reaction mixture was mixed with water and diluted with ethyl acetate. The phases were separated and the aqueous phase was extracted with ethyl acetate (1×). The combined organic phase was washed with water (1×) and saturated sodium chloride solution (1×), dried over magnesium sulfate and filtered, and the solvent was evaporated in vacuo. The resulting residue was purified by preparative MPLC (ISCO Companion, 12 g NP cartridge) with dichloromethane/methanol (10-70%) as eluent. 497 mg (0.99 mmol, 66%) of the title compound were obtained as a colorless solid.

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate (1×)
  4. washThe combined organic phase was 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 resulting residue was purified by preparative MPLC (ISCO Companion, 12 g NP cartridge) with dichloromethane/methanol (10-70%) as eluent

Sources & evidence

ORD record
ord-cfe978cadb0344519d16a6325951b2dc
Source dataset
uspto-grants-2014_04
Patent number
US08703775B2

Reaction notes

Loading…