Sodium Carbonate → 4-{4-[3-(4-carbamoyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 85052Notes

Reaction equation

HRID 85052 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:19]=[CH:18][C:14]([C:15]([NH2:17])=[O:16])=[CH:13][CH:12]=3)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[C:30]([O:34][C:35]([N:37]1[CH2:42][CH2:41][N:40]([C:43](=[O:59])[C:44]2[CH:49]=[CH:48][C:47](B3OC(C)(C)C(C)(C)O3)=[CH:46][CH:45]=2)[CH2:39][CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31].C([O-])([O-])=O.[Na+].[Na+]>CC#N.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:30]([O:34][C:35]([N:37]1[CH2:42][CH2:41][N:40]([C:43](=[O:59])[C:44]2[CH:45]=[CH:46][C:47]([C:2]3[CH:3]=[C:4]4[C:10]([C:11]5[CH:12]=[CH:13][C:14]([C:15](=[O:16])[NH2:17])=[CH:18][CH:19]=5)=[CH:9][NH:8][C:5]4=[N:6][CH:7]=3)=[CH:48][CH:49]=2)[CH2:39][CH2:38]1)=[O:36])([CH3:33])([CH3:31])[CH3:32]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 17749917(4-(4-BOC-piperazine-1-carbonyl)phenyl)boronic acid pinacol esterHCID 667786584-[5-bromo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-benzamide

Product 1

HCID 667796424-{4-[3-(4-carbamoyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoyl}-piperazine-1-carboxylic acid tert-butyl esterYield 46%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

4-[5-Bromo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-benzamide (Intermediate CA, 200 mg, 0.425 mmol), 4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoyl]-piperazine-1-carboxylic acid tert-butyl ester (212 mmg, 0.51 mmol) and dichlorobis(triphenylphosphine)palladium (II) (15 mg, 0.021 mmol) were combined in CH3CN (5 ml) and 1 M Na2CO3 (5 ml) and reacted in a microwave reactor at 150° C. for 10 min. The mixture was filtered, water was added, extracted with EtOAc and purified by silica gel chromatography using 0-8% MeOH:DCM. The title compound was obtained in 46% yield (102 mg). 1H NMR (DMSO-d6, 300 MHz): δ 12.2 (bs, 1H), 8.63 (d, J=1.1 Hz, 1H), 8.54 (d, J=1.1 Hz, 1H), 8.08 (s, 1H), 7.98 (bs, 1H), 7.96 (d, J=5.1 Hz, 2H), 7.89 (m, 4H), 7.54 (d, J=4.9 Hz, 2H), 7.32 (bs, 1H), 3.6 (bs, 2H), 3.4 (bs), 1.41 (s, 9H).

Workup

  1. filtrationThe mixture was filtered
  2. additionwater was added
  3. extractionextracted with EtOAc
  4. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-58a224b780c54f95b8f91e5448956a15
Source dataset
uspto-grants-2014_09
Patent number
US08846909B2

Reaction notes

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