Potassium Carbonate → (5-{2-[(Benzyl-cyclopropanecarbonyl-amino)-methyl]-4-cyano-phenyl}-pyridin-3-yl)-acetic acid ethyl ester

HRID 554592Notes

Reaction equation

HRID 554592 reaction equation
[CH2:1]([N:8]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]#[N:22])[CH:18]=[CH:17][C:16]=1B1OC(C)(C)C(C)(C)O1)[C:9]([CH:11]1[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:32]([O:34][C:35](=[O:44])[CH2:36][C:37]1[CH:38]=[N:39][CH:40]=[C:41](Br)[CH:42]=1)[CH3:33].C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.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>[CH2:32]([O:34][C:35](=[O:44])[CH2:36][C:37]1[CH:38]=[N:39][CH:40]=[C:41]([C:16]2[CH:17]=[CH:18][C:19]([C:21]#[N:22])=[CH:20][C:15]=2[CH2:14][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:9]([CH:11]2[CH2:12][CH2:13]2)=[O:10])[CH:42]=1)[CH3:33]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 54116619Ethyl 2-(5-bromopyridin-3-yl)acetateHCID 67212390Cyclopropanecarboxylic acid benzyl-[5-cyano-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-amide

Product 1

HCID 67212964(5-{2-[(Benzyl-cyclopropanecarbonyl-amino)-methyl]-4-cyano-phenyl}-pyridin-3-yl)-acetic acid ethyl ester

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

Cyclopropanecarboxylic acid benzyl-[5-cyano-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-amide (1.33 g, 3.2 mmol), (5-bromo-pyridin-3-yl)-acetic acid ethyl ester (1.02 g, 4.2 mmol), and potassium carbonate (1.55 g, 11.2 mmol) were combined in DME (40 mL) and H2O (30 mL), and the solution was purged with N2 for 15 minutes. Tetrakis(triphenylphosphine)palladium(0) (0.370 g, 0.35 mmol) was added, and the reaction was stirred at 70° C. for 1 hour. The mixture was diluted with H2O and 1N aqueous HCl (15 mL), and extracted with EtOAc. The combined organic layers were concentrated and purified by preparative HPLC to give (5-{2-[(benzyl-cyclopropanecarbonyl-amino)-methyl]-4-cyano-phenyl}-pyridin-3-yl)-acetic acid ethyl ester, as well as the some of the hydrolyzed ester product.

Workup

  1. customH2O (30 mL), and the solution was purged with N2 for 15 minutes
  2. extractionextracted with EtOAc
  3. concentrationThe combined organic layers were concentrated
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-bb027aabd8bb46da8616333f5d0354e0
Source dataset
uspto-grants-2011_11
Patent number
US08049015B2

Reaction notes

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