Nicotinic Acid → N-(4-(4-benzylpiperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide

HRID 79590Notes

Reaction equation

HRID 79590 reaction equation
Cl[C:2]1[CH:7]=C[C:5]([C@@H:8](CNC(C)C)[C:9]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]4[NH:23][CH:24]=[C:25]([NH:26]C(=O)CCC)[C:18]=34)[CH2:13][CH2:12]2)=O)=[CH:4][CH:3]=1.[C:37]([OH:45])(=O)[C:38]1[CH:43]=[CH:42][CH:41]=[N:40][CH:39]=1.C(N(CC)CC)C.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CO.[Li+].[OH-]>[CH2:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]3[NH:23][CH:24]=[C:25]([NH:26][C:37](=[O:45])[C:38]4[CH:43]=[CH:42][CH:41]=[N:40][CH:39]=4)[C:18]=23)[CH2:13][CH2:12]1)[C:8]1[CH:7]=[CH:2][CH:3]=[CH:4][CH:5]=1

Participants

8

Reactant 4

HCID 938Nicotinic AcidHCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 44199250(S)-N-(4-(4-(2-(4-chlorophenyl)-3-(isopropylamino)propanoyl)piperazin-1-yl)-1H-pyrrolo [2,3-b]pyridin-3-yl)butyramide

Product 1

HCID 68760686N-(4-(4-benzylpiperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamideYield 59.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3939Lithium HydroxideSolventHCID 6228DimethylformamideSolvent

Procedure

Crude 4-(4-benzylpiperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-amine (0.200 g, 0.651 mmol, see Example 25), nicotinic acid (0.0961 g, 0.781 mmol) and triethylamine (0.453 mL, 3.25 mmol) were placed in DMF (3 mL) at room temperature. Triethylamine (0.453 mL, 3.25 mmol) was then added, and the reaction was stirred for 1 hour at room temperature. The reaction was then diluted with MeOH (5 mL), and 3M LiOH (0.5 mL) was added and stirred for 10 minutes. The reaction was then poured into saturated Na2CO3 and extracted into DCM. The organic fractions were combined, dried, filtered and concentrated to give a crude residue that was purified by column chromatography (500:20-500:30 DCM:MeOH) to give N-(4-(4-benzylpiperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (0.160 g, 59.6% yield).

Workup

  1. additionwas added
  2. stirringstirred for 10 minutes
  3. extractionextracted into DCM
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude residue that
  8. customwas purified by column chromatography (500:20-500:30 DCM:MeOH)

Sources & evidence

ORD record
ord-28b8a1ddc7934aa48fe7cedccbd0a135
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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