Sodium Bicarbonate → N-(3,4-Dimethoxybenzyl)-5-(3,5-dimethylphenyl)-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide

HRID 1675938Notes

Reaction equation

HRID 1675938 reaction equation
Cl[C:2]1[N:21]=[CH:20][C:19]([C:22]2[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([CH3:29])[CH:23]=2)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=1)=[O:5].[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1.C(=O)(O)[O-].[Na+]>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>[CH3:17][O:16][C:10]1[CH:9]=[C:8]([CH:13]=[CH:12][C:11]=1[O:14][CH3:15])[CH2:7][NH:6][C:4](=[O:5])[C:3]1[CH:18]=[C:19]([C:22]2[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([CH3:29])[CH:23]=2)[CH:20]=[N:21][C:2]=1[C:34]1[CH:33]=[N:32][N:31]([CH3:30])[CH:35]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 585390332-Chloro-N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)nicotinamide

Product 1

HCID 25224401N-(3,4-Dimethoxybenzyl)-5-(3,5-dimethylphenyl)-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

To a solution of 2-chloro-N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)nicotinamide (1-3, 50.0 mg, 0.122 mmol)) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (25.3 mg, 0.122 mmol) in dioxanes (3 mL) was added tetrakis(triphenylphosphine)palladium(0) (7.03 mg, 6.08 μmol) and 2 N aqueous sodium bicarbonate solution (0.304 mL, 0.608 mmol). Under microwave heating the deoxygenated mixture was held at 160° C. for 1 h. The reaction mixture was filtered and concentrated to dryness. A solid residue was triturated with ethyl acetate (4 mL), collected by filtration, washed with water (10 mL) and air dried to afford N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide (1-4). 1H NMR (300 MHz, DMSO) δ 9.09 (t, 1H, J=5.8 Hz), 8.87 (d, 1H, J=1.8 Hz), 7.92 (d, 1H, J=1.8 Hz), 7.82 (d, 1H, J=9.8 Hz), 7.39 (s, 2H), 7.06 (s, 1H), 6.92 (m, 3H), 4.29 (d, 2H, J=5.3 Hz), 3.74 (m, 6H), 3.32 (s, 3H), 2.35 (s, 3H). HRMS m/z (M+H) 457.2242 found, 457.2234 required.

Workup

  1. temperatureUnder microwave heating the deoxygenated mixture
  2. filtrationThe reaction mixture was filtered
  3. concentrationconcentrated to dryness
  4. customA solid residue was triturated with ethyl acetate (4 mL)
  5. filtrationcollected by filtration
  6. washwashed with water (10 mL) and air
  7. customdried

Sources & evidence

ORD record
ord-f0c641c19dce47228119cef85acf41b6
Source dataset
uspto-grants-2011_08
Patent number
US08003797B2

Reaction notes

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