Phenylboronic Acid → N-(5-phenyl-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide

HRID 79620Notes

Reaction equation

HRID 79620 reaction equation
Br[C:2]1[C:3]([N:20]2[CH2:25][CH2:24][N:23]([C:26](=[O:36])[CH2:27][NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:22][CH2:21]2)=[C:4]2[C:10]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[C:37]1(B(O)O)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>O1CCOCC1.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:12]([NH:11][C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:3]=2[N:20]2[CH2:25][CH2:24][N:23]([C:26](=[O:36])[CH2:27][NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:22][CH2:21]2)[NH:8][CH:9]=1)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=1.[C:37]1([C:2]2[C:3]([N:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)=[C:4]3[C:10]([NH:11][C:12](=[O:19])[C:13]4[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=4)=[CH:9][NH:8][C:5]3=[N:6][CH:7]=2)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

7

Reactant 2

HCID 66827Phenylboronic AcidHCID 68781630tert-butyl 2-(4-(5-bromo-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-oxoethylcarbamate

Product 2

HCID 68760217N-(5-phenyl-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamideYield 31%HCID 68781181HCID 68781181, compoundYield 15%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

tert-Butyl 2-(4-(5-bromo-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-oxoethylcarbamate (0.090 g, 0.16 mmol) and phenylboronic acid (0.039 g, 0.32 mmol) were placed in dioxane (1.5 mL) and degassed for 30 minutes. A 20% Na2CO3 (0.5 mL) solution was then added, followed by the addition of PS-Pd(PPh3)4 (0.081 g, 0.0081 mmol). The reaction was then heated in a microwave at 150° C. for 1 hour. The reaction was next diluted with DCM and filtered to remove the catalyst The reaction was then purified by prep HPLC to give a mixture of tert-butyl 2-(4-(3-(nicotinamido)-5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-oxoethylcarbamate (0.013 g, 15% yield) and N-(5-phenyl-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (0.020 g, 31% yield).

Workup

  1. customdegassed for 30 minutes
  2. additionA 20% Na2CO3 (0.5 mL) solution was then added
  3. filtrationfiltered
  4. customto remove the catalyst The reaction
  5. customwas then purified by prep HPLC
  6. customto give

Sources & evidence

ORD record
ord-860efa27a51f4dd4820a766f5f8e2dfb
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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