1-Hydroxybenzotriazole → 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 1925575Notes

Reaction equation

HRID 1925575 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.[NH:23]1[C:27]2[N:28]=[CH:29][CH:30]=[C:31]([C:32](O)=[O:33])[C:26]=2[CH:25]=[CH:24]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:32]([C:31]3[C:26]4[CH:25]=[CH:24][NH:23][C:27]=4[N:28]=[CH:29][CH:30]=3)=[O:33])[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 224774261H-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 445484941H-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 63.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 100 ml round-bottomed flask, a mixture of 51 mg of 5-(3H-imidazo[4,5-c]pyridin-2-yl)-9H-pyrrolo[1,2-a]indol-9-ylamine obtained according to the preceding stage, 28 mg of 1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid (which can be obtained according to WO 2003/000688), 37 mg of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) and 26 mg of 1-hydroxybenzotriazole (HOBt) in 5 ml of dimethylformamide is stirred for 4 hours under argon at ambient temperature. The reaction medium is evaporated to dryness under vacuum. The residue is triturated from 20 ml of water and then filtered. The solid is washed with a saturated solution of sodium bicarbonate and taken up in a mixture of dichloromethane and methanol, and the solution is evaporated to dryness under vacuum. The residue is chromatographed on silica gel (15-40 μm), elution being carried out with a mixture of dichloromethane and methanol (98/2 v/v). 47 mg of 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. customThe reaction medium is evaporated to dryness under vacuum
  3. customThe residue is triturated from 20 ml of water
  4. filtrationfiltered
  5. washThe solid is washed with a saturated solution of sodium bicarbonate
  6. additiontaken up in a mixture of dichloromethane and methanol
  7. customthe solution is evaporated to dryness under vacuum
  8. customThe residue is chromatographed on silica gel (15-40 μm), elution
  9. additionbeing carried out with a mixture of dichloromethane and methanol (98/2 v/v)

Sources & evidence

ORD record
ord-711b4c6443424bff99d1ed9d6ce11056
Source dataset
uspto-grants-2012_05
Patent number
US08178687B2

Reaction notes

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