Potassium Carbonate → N-isobutyl-2-methyl-2-(4-(1-methyl-1H-pyrrol-2-yl)phenyl)propanamide

HRID 1175609Notes

Reaction equation

HRID 1175609 reaction equation
[CH2:1]([NH:5][C:6](=[O:25])[C:7]([CH3:24])([C:9]1[CH:14]=[CH:13][C:12](B2OC(C)(C)C(C)(C)O2)=[CH:11][CH:10]=1)[CH3:8])[CH:2]([CH3:4])[CH3:3].C([O-])([O-])=O.[K+].[K+].[CH3:32][N:33]1[CH:37]=[CH:36][CH:35]=[C:34]1Br>COCCOC.O.[Cl-].[Na+].O.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>[CH2:1]([NH:5][C:6](=[O:25])[C:7]([CH3:8])([C:9]1[CH:10]=[CH:11][C:12]([C:34]2[N:33]([CH3:32])[CH:37]=[CH:36][CH:35]=2)=[CH:13][CH:14]=1)[CH3:24])[CH:2]([CH3:3])[CH3:4]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 10931723N-methyl-2-bromopyrroleHCID 68776318N-isobutyl-2-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanamide

Product 1

HCID 16005233N-isobutyl-2-methyl-2-(4-(1-methyl-1H-pyrrol-2-yl)phenyl)propanamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of N-isobutyl-2-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanamide (example 23a) (19.04 g, 55.14 mmol), K2CO3 (22.86 g, 165.4 mmol), and N-methyl-2-bromopyrrole (7.50 g, 93.74 mmol) in DME/H2O (4/1, 300 mL) was added Pd(PPh3)4 (3.20 g, 2.76 mmol) at RT under argon and the reaction mixture was stirred at 85° C. overnight. After it was cooled down to room temperature, the reaction mixture was diluted with brine, and extracted with EtOAc (3×). The combined organic layers were washed with brine, and dried over Na2SO4. After evaporation of the solvent under reduced pressure, the residue was purified twice by chromatography on silica gel eluting with EtOAc/Hexanes (1/9) to give the title compound as off-white white solid, which was further purified by recrystallization from hexanes, and dried under vacuum overnight. mp: 59-60° C. 1H NMR (400 MHz, DMSO-d6) δ 7.35 (d, J=7.2 Hz, 2H), 7.31 (d, J=7.2 Hz, 2H), 6.79 (m, 1H), 6.09 (m, 1H), 6.01 (m, 1H), 3.60 (s, 3H), 2.82 (t, J=6.4 Hz, 2H), 1.7 (m, 1H), 1.44 (s, 6H), 0.2 (d, J=7.2 Hz, 6H). MS 299 (MH+).

Workup

  1. temperatureAfter it was cooled down to room temperature
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. customAfter evaporation of the solvent under reduced pressure
  6. customthe residue was purified twice by chromatography on silica gel eluting with EtOAc/Hexanes (1/9)

Sources & evidence

ORD record
ord-86a7a39720a14bb3be4294bf0ec477d5
Source dataset
uspto-grants-2010_11
Patent number
US07842324B2

Reaction notes

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