1-Hydroxybenzotriazole → HCID 44548493, compound

HRID 1925570Notes

Reaction equation

HRID 1925570 reaction equation
C(O)(=O)C.[N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[C:7]([C:15]2[C:23]3[N:22]4[CH:24]=[CH:25][CH:26]=[C:21]4[CH:20]([NH2:27])[C:19]=3[CH:18]=[CH:17][CH:16]=2)[CH:6]=1.[NH:28]1[C:32]2[N:33]=[CH:34][CH:35]=[C:36]([C:37](O)=[O:38])[C:31]=2[CH:30]=[CH:29]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[C:7]([C:15]2[C:23]3[N:22]4[CH:24]=[CH:25][CH:26]=[C:21]4[CH:20]([NH:27][C:37]([C:36]4[C:31]5[CH:30]=[CH:29][NH:28][C:32]=5[N:33]=[CH:34][CH:35]=4)=[O:38])[C:19]=3[CH:18]=[CH:17][CH:16]=2)[CH:6]=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 67299291HCID 67299291, compound

Product 1

HCID 44548493HCID 44548493, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 100 ml round-bottomed flask under argon, a mixture of 116 mg of 5-quinolin-3-yl-9H-pyrrolo[1,2-a]indol-9-ylamine acetate obtained according to the preceding stage, 63 mg of 1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid (which can be obtained according to WO 2003/000688), 82 mg of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) and 58 mg of 1-hydroxybenzotriazole (HOBt) in 7.5 ml of dimethylformamide is stirred at ambient temperature for 18 hours. The reaction medium is evaporated to dryness under vacuum, 50 ml of water are added to the residue, and the suspension is stirred for 1 hour. The solid is filtered and washed with water, then with a saturated solution of sodium bicarbonate and again with water. The resulting product is spin-filter-dried overnight and then the solid is taken up in a mixture of methanol and dichloromethane (10/90 v/v), and the solvent is evaporated to dryness under vacuum. The residue is chromatographed on silica gel (15-40 μm), elution being carried out with a mixture of methanol and dichloromethane (3/97 v/v). 53 mg of 1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid (5-quinolin-3-yl-9H-pyrrolo[1,2-a]indol-9-yl)amide are obtained in the form of a beige solid, the characteristics of which are the following:

Workup

  1. customobtained
  2. customThe reaction medium is evaporated to dryness under vacuum, 50 ml of water
  3. additionare added to the residue
  4. stirringthe suspension is stirred for 1 hour
  5. filtrationThe solid is filtered
  6. washwashed with water
  7. customThe resulting product is spin-filter-dried overnight
  8. additionthe solid is taken up in a mixture of methanol and dichloromethane (10/90 v/v)
  9. customthe solvent is evaporated to dryness under vacuum
  10. customThe residue is chromatographed on silica gel (15-40 μm), elution
  11. additionbeing carried out with a mixture of methanol and dichloromethane (3/97 v/v)

Sources & evidence

ORD record
ord-0bb2418f0ea0440d97a23c626f5e00dc
Source dataset
uspto-grants-2012_05
Patent number
US08178687B2

Reaction notes

Loading…