Cesium carbonate → 4-(2-Chloro-5-methylpyrimidin-4-ylamino)-2-chlorobenzonitrile

HRID 1097082Notes

Reaction equation

HRID 1097082 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH3:9])=[CH:4][N:3]=1.Br[C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[C:13]([Cl:19])[CH:12]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:11]2[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[C:13]([Cl:19])[CH:12]=2)[C:5]([CH3:9])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 43021752-Chloro-5-methylpyrimidin-4-amineHCID 70104204-Bromo-2-chlorobenzonitrile

Product 1

HCID 575164844-(2-Chloro-5-methylpyrimidin-4-ylamino)-2-chlorobenzonitrile

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-chloro-5-methylpyrimidin-4-amine (144 mg, 1.0 mmol) in 1,4-dioxane (20 mL) was added 4-bromo-2-chlorobenzonitrile (217 mg, 1.0 mmol), Cs2CO3 (1.3 g, 4.0 mmol), Pd2(dba)3 (91 mg, 0.1 mmol), and 4,5-bis(diphenylphosphino)-9,9-dimethyxanthene (Xant Phos, 173 mg, 0.3 mmol). The mixture was heated under reflux for 4 h under Ar. The solid was filtered off and the filtrate washed with brine (1×100 mL). The organic solution was separated and dried (Na2SO4). The solvent was removed until 5 mL and hexane (100 mL) was added, the solid was collected by filtration. The crude product, the title intermediate 26, was used for next reaction without further purification.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 4 h under Ar
  3. filtrationThe solid was filtered off
  4. washthe filtrate washed with brine (1×100 mL)
  5. customThe organic solution was separated
  6. dry with materialdried (Na2SO4)
  7. customThe solvent was removed until 5 mL and hexane (100 mL)
  8. additionwas added
  9. filtrationthe solid was collected by filtration
  10. customThe crude product, the title intermediate 26, was used for next reaction without further purification

Sources & evidence

ORD record
ord-7ac5bd1ff3a247df9a412444d4b6df57
Source dataset
uspto-grants-2012_03
Patent number
US08138199B2

Reaction notes

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