Ethylenediamine → 5-(1H-Indol-2-yl)-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (1-benzyl-1H-pyrazol-4-yl)-amide

HRID 1406391Notes

Reaction equation

HRID 1406391 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:17]1[C:18](=[O:46])[N:19](COCC[Si](C)(C)C)[CH:20]=[C:21]([C:23](=[O:37])[NH:24][C:25]2[CH:26]=[N:27][N:28]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:29]=2)[CH:22]=1)=O)(C)(C)C.NCCN.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH2:30]([N:28]1[CH:29]=[C:25]([NH:24][C:23]([C:21]2[CH:22]=[C:17]([C:9]3[NH:8][C:16]4[C:11]([CH:10]=3)=[CH:12][CH:13]=[CH:14][CH:15]=4)[C:18](=[O:46])[NH:19][CH:20]=2)=[O:37])[CH:26]=[N:27]1)[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 2724141Tetrabutylammonium FluorideHCID 581173962-[5-(1-Benzyl-1H-pyrazol-4-ylcarbamoyl)-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester2×

Product 1

HCID 668547185-(1H-Indol-2-yl)-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (1-benzyl-1H-pyrazol-4-yl)-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Intermediate (1d), 2-[5-(1-benzyl-1H-pyrazol-4-ylcarbamoyl)-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]indole-1-carboxylic acid tert-butyl ester (315 mg, 0.492 mmol) was stirred in tetrahydrofuran (15 mL) and 1,2-diaminoethane (89 mg, 98 ul, 1.48 mmol) was added followed by tetrabutylammonium fluoride solution 1.0M in tetrahydrofuran (2.46 mL, 2.46 mmol). The reaction mixture was heated at reflux for 18 hours, and cooled to ambient temperature. The reaction mixture was concentrated in vacuo. The residue was partitioned between water and dichloromethane, and the organic layer was separated. The aqueous was extracted with a further portion of dichloromethane and the combined dichloromethane layers were washed with water (×3) dried (Na2SO4) and concentrated in vacuo. The resultant crude product was purified by flash chromatography on SiO2 eluting with dichloromethane—8% methanol/dichloromethane (gradient) to afford a solid. This solid was triturated with diethyl ether to afford the desired title compound as a yellow solid, 41 mg, 20%.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 18 hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customThe residue was partitioned between water and dichloromethane
  5. customthe organic layer was separated
  6. extractionThe aqueous was extracted with a further portion of dichloromethane
  7. washthe combined dichloromethane layers were washed with water (×3)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe resultant crude product was purified by flash chromatography on SiO2 eluting with dichloromethane—8% methanol/dichloromethane (gradient)
  11. customto afford a solid
  12. customThis solid was triturated with diethyl ether

Sources & evidence

ORD record
ord-d4187dc170aa43e782be01ccb4aabe04
Source dataset
uspto-grants-2014_12
Patent number
US08916591B2

Reaction notes

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