1-Hydroxybenzotriazole → 6-chloro-1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid [5-(3H-imidazo[4,5-c]pyridin-2-yl)-9H-pyrrolo[1,2-a]indol-9-yl]amide

HRID 1925577

Reaction equation

HRID 1925577 reaction equation
[N:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[NH:3][C:2]=1[C:10]1[C:18]2[N:17]3[CH:19]=[CH:20][CH:21]=[C:16]3[CH:15]([NH2:22])[C:14]=2[CH:13]=[CH:12][CH:11]=1.[Cl:23][C:24]1[CH:25]=[C:26]([C:33](O)=[O:34])[C:27]2[CH:32]=[CH:31][NH:30][C:28]=2[N:29]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[N:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[NH:3][C:2]=1[C:10]1[C:18]2[N:17]3[CH:19]=[CH:20][CH:21]=[C:16]3[CH:15]([NH:22][C:33]([C:26]3[C:27]4[CH:32]=[CH:31][NH:30][C:28]=4[N:29]=[C:24]([Cl:23])[CH:25]=3)=[O:34])[C:14]=2[CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 533995756-chloro-1H-pyrrolo[2,3-b]pyridine-4-carboxylic acidHCID 670728065-(3H-imidazo[4,5-c]pyridin-2-yl)-9H-pyrrolo[1,2-a]indol-9-ylamine

Product 1

HCID 445484956-chloro-1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid [5-(3H-imidazo[4,5-c]pyridin-2-yl)-9H-pyrrolo[1,2-a]indol-9-yl]amideYield 9.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 100 ml round-bottomed flask, a mixture of 69 mg of 5-(3H-imidazo[4,5-c]pyridin-2-yl)-9H-pyrrolo[1,2-a]indol-9-ylamine obtained according to stage 4 of Example 3, 48 mg of 6-chloro-1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid obtained according to the preceding stage, 51 mg of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) and 36 mg of 1-hydroxybenzotriazole (HOBt) in 5 ml of dimethylformamide is stirred for 3 hours under argon at ambient temperature. The reaction medium is evaporated to dryness under vacuum and the residue is chromatographed on silica gel (15-40 μm), elution being carried out with a gradient of methanol (4% to 6% v/v) in dichloromethane. The valuable fractions are combined and evaporated to dryness under vacuum, the residue is triturated from a solution of sodium bicarbonate and filtered, and the solid is washed with water. The precipitate is dissolved in methanol and the solvent is evaporated to dryness under vacuum. 11 mg of 6-chloro-1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid [5-(3H-imidazo[4,5-c]pyridin-2-yl)-9H-pyrrolo[1,2-a]indol-9-yl]amide are obtained in the form of a solid, the characteristics of which are the following:

Workup

  1. customobtained
  2. customobtained
  3. customThe reaction medium is evaporated to dryness under vacuum
  4. customthe residue is chromatographed on silica gel (15-40 μm), elution
  5. customevaporated to dryness under vacuum
  6. customthe residue is triturated from a solution of sodium bicarbonate
  7. filtrationfiltered
  8. washthe solid is washed with water
  9. dissolutionThe precipitate is dissolved in methanol
  10. customthe solvent is evaporated to dryness under vacuum

Sources & evidence

ORD record
ord-5cec978aac5d4485871677c7fb835490
Source dataset
uspto-grants-2012_05
Patent number
US08178687B2

Linked notes

Loading…