Potassium Phosphate, Tribasic → Methyl 4-(3-amino-1,2,4-triazin-6-yl)-2-chlorobenzoate

HRID 452032

Reaction equation

HRID 452032 reaction equation
Br[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[N:4][CH:3]=1.[Cl:9][C:10]1[CH:11]=[C:12](B(O)O)[CH:13]=[CH:14][C:15]=1[C:16]([O:18][CH3:19])=[O:17].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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>[NH2:8][C:5]1[N:6]=[N:7][C:2]([C:12]2[CH:13]=[CH:14][C:15]([C:16]([O:18][CH3:19])=[O:17])=[C:10]([Cl:9])[CH:11]=2)=[CH:3][N:4]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 153325646-Bromo-1,2,4-triazin-3-amineHCID 230053353-Chloro-4-(methoxycarbonyl)benzeneboronic acid

Product 1

HCID 57516524Methyl 4-(3-amino-1,2,4-triazin-6-yl)-2-chlorobenzoateYield 55.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
82 °C

Procedure

To a mixture of 6-bromo-1,2,4-triazin-3-amine (Step 1, 1.0 g, 5.7 mmol) and [3-chloro-4-(methoxycarbonyl)phenyl]boronic acid (1.5 g, 6.8 mmol) (VMR, Cat. #100013-404) in 1,4-dioxane (22 mL) was added a solution of potassium phosphate (2.4 g, 11 mmol) in water (5.1 mL). The mixture was degassed by purging nitrogen for 10 min. To the mixture was added tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.17 mmol) and again was degassed with nitrogen. The mixture was stirred and heated at 82° C. (an oil bath) for 1 h. The mixture was cooled to r.t., diluted with water, stirred for 30 min, and a grey solid formed. The solid was isolated by filtration, rinsed several times with water, and dried in air. The solid was then triturated sequentially with hexanes, dichloromethane-hexanes (1:1), and hexanes to afford the desired product (840 mg, 55.54%). LCMS (M+H)+: m/z=264.9/267.0.

Workup

  1. customThe mixture was degassed
  2. customby purging nitrogen for 10 min
  3. customagain was degassed with nitrogen
  4. temperatureThe mixture was cooled to r.t.
  5. additiondiluted with water
  6. stirringstirred for 30 min
  7. customa grey solid formed
  8. customThe solid was isolated by filtration
  9. washrinsed several times with water
  10. customdried in air
  11. customThe solid was then triturated sequentially with hexanes, dichloromethane-hexanes (1:1), and hexanes

Sources & evidence

ORD record
ord-89edc7b3b08c46acb48b7bfa97a9e51a
Source dataset
uspto-grants-2013_07
Patent number
US08487096B2

Linked notes

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