Pyridine → N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-cyanobenzamide

HRID 1364947Notes

Reaction equation

HRID 1364947 reaction equation
[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1.N1C=CC=CC=1.[C:21]([C:23]1[CH:31]=[CH:30][C:26]([C:27](Cl)=[O:28])=[CH:25][CH:24]=1)#[N:22]>ClCCl.C1COCC1.CO>[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:27](=[O:28])[C:26]2[CH:30]=[CH:31][C:23]([C:21]#[N:22])=[CH:24][CH:25]=2)=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1

Participants

7

Reactant 3

HCID 1049PyridineHCID 801724-Cyanobenzoyl chlorideHCID 401519254-Chloro-3-(pyridin-2-yl)aniline

Product 1

HCID 66877347N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-cyanobenzamideYield 81%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-Chloro-3-(pyridin-2-yl)aniline (687 mg, 3.36 mmol) was dissolved in dichloromethane (8.0 ml) and THF (8.0 ml), treated with pyridine (0.33 ml, 4.0 mmol), and cooled to 0° C. 4-Cyanobenzoyl chloride (612 mg, 3.7 mmol) was added and the reaction was stirred for 1.0 hour. The reaction was diluted with dichloromethane and methanol was added to dissolve all solids. The solution was washed with water once, brine once, dried with MgSO4, and evaporated to an orange solid which was purified by silica gel flash column chromatography (50% ethyl acetate/50% hexanes) to afford 908 mg of N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-cyanobenzamide as a yellow solid. N-(4-Chloro-3-(pyridin-2-yl)phenyl)-4-cyanobenzamide (500 mg, 1.5 mmol) was slurried in ethanol (75 ml) and heated until just dissolved. The solution was cooled in an ice bath, and saturated with HCl gas. The solution was heated briefly to 70° C. to dissolve precipitated solids, cooled in an ice bath, and resaturated with HCl gas. The solution was then stored at 0° C. for 18 hours. The solution was saturated again with HCl gas, heated to 70° C. until all solids dissolved, cooled to 0° C., resaturated with HCl gas, and stored at 0° C. for 18 hours. Finally, nitrogen gas was bubbled through the solution for 1.0 hour, and the solution was evaporated to dryness. The residue was dissolved in methanol, treated with MP-carbonate (2.57 g) and stirred 30 min. The solution was filtered to afford a neutral, methanolic solution of ethyl 4-(4-chloro-3-(pyridin-2-yl)phenylcarbamoyl)benzimidate, which was diluted with enough methanol to make a 0.075 M solution.

Workup

  1. additionwas added
  2. dissolutionto dissolve all solids
  3. washThe solution was washed with water once
  4. dry with materialbrine once, dried with MgSO4
  5. customevaporated to an orange solid which
  6. customwas purified by silica gel flash column chromatography (50% ethyl acetate/50% hexanes)

Sources & evidence

ORD record
ord-90eb3cfaee2c4a9c9a43553c1d042205
Source dataset
uspto-grants-2011_02
Patent number
US07888364B2

Reaction notes

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