Sodium Carbonate → N-(3-(trifluoromethyl)benzyl)-2-(2-amino-5-chlorophenyl)-isonicotinamide

HRID 625305Notes

Reaction equation

HRID 625305 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([CH:9]2OC(C)(C)C(C)(C)O2)[CH:3]=1.[F:18][C:19]([F:38])([F:37])[C:20]1[CH:21]=[C:22]([CH:34]=[CH:35][CH:36]=1)[CH2:23][NH:24][C:25](=[O:33])[C:26]1[CH:31]=C[N:29]=[C:28](Br)[CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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>[F:18][C:19]([F:37])([F:38])[C:20]1[CH:21]=[C:22]([CH:34]=[CH:35][CH:36]=1)[CH2:23][NH:24][C:25](=[O:33])[C:26]1[CH:27]=[CH:28][N:29]=[C:9]([C:4]2[CH:3]=[C:2]([Cl:1])[CH:7]=[CH:6][C:5]=2[NH2:8])[CH:31]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 665875304-Chloro-2-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)benzenamineHCID 867059444-Pyridinecarboxamide, 2-bromo-N-[[3-(trifluoromethyl)phenyl]methyl]-

Product 1

HCID 66586773N-(3-(trifluoromethyl)benzyl)-2-(2-amino-5-chlorophenyl)-isonicotinamideYield 55%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

Into a 50-mL round bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-chloro-2-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)benzenamine (300 mg, 1.17 mmol, 1.00 equiv) in ethylene glycol dimethyl ether (15 mL), N-(3-(trifluoromethyl)benzyl)-2-bromoisonicotinamide (432 mg, 1.20 mmol, 1.00 equiv), a solution of sodium carbonate (636 mg, 6.00 mmol, 5.00 equiv) in water (3.0 mL), and Pd(PPh3)4 (138 mg, 0.12 mmol, 0.10 equiv). The resulting solution was stirred for 2 h at 85° C. in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 10 mL of water. The resulting solution was extracted with 3×10 mL of ethyl acetate and the organic layers combined, and washed with brine. The mixture was dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with petroleum ether/ethyl acetate (10:1-5:1). The product was obtained as 260 mg (55%) of a yellow solid.

Workup

  1. customInto a 50-mL round bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. additionThe resulting solution was diluted with 10 mL of water
  5. extractionThe resulting solution was extracted with 3×10 mL of ethyl acetate
  6. washwashed with brine
  7. dry with materialThe mixture was dried over sodium sulfate
  8. concentrationconcentrated under vacuum
  9. washeluted with petroleum ether/ethyl acetate (10:1-5:1)

Sources & evidence

ORD record
ord-8ffdf5bd6bc54ea786db3d417ff4b708
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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