Hydrochloric Acid → 4-((4-Amino-5,6-dichloropyrimidin-2-yl)amino)benzonitrile

HRID 41367Notes

Reaction equation

HRID 41367 reaction equation
[NH2:1][C:2]1[C:7]([Cl:8])=[C:6]([Cl:9])[N:5]=[C:4](Cl)[N:3]=1.[NH2:11][C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=1.CN1CCCC1=O.Cl>C(OCC)C.O1CCOCC1>[NH2:1][C:2]1[C:7]([Cl:8])=[C:6]([Cl:9])[N:5]=[C:4]([NH:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=2)[N:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 13387N-methyl-2-pyrrolidone2×HCID 133964-AminobenzonitrileHCID 158501962,5,6-Trichloropyrimidin-4-amine

Product 1

HCID 221700984-((4-Amino-5,6-dichloropyrimidin-2-yl)amino)benzonitrileYield 6.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
145 °C

Procedure

To a flask under Argon was added 4-amino-2,5,6-trichloropyrimidine (0.08564 mol), 4-amino-benzonitrile (0.1071 mol), 1-methyl-2-pyrrolidinone (17 ml) and HCl in diethylether (1M; 85.6 ml). The mixture was placed in an oil bath at 130° C. under a stream of nitrogen until the ether was gone. An additional 10 ml of 1-methyl-2-pyrrolidinone was added. The mixture was heated at 145° C. for 16 hours under argon. 1,4-Dioxane was added. The mixture was refluxed, cooled, then filtered. The filtrate was evaporated. The residue was dissolved in CH2Cl2, washed with 1 N NaOH, then filtered. The solid was dissolved in 2-propanone, evaporated onto silica gel, and chromatographed using 1-3% 2-propanone in hexane as eluent. The pure fractions were collected and the solvent was evaporated, yielding 1.63 g (6.8%) of 4-[(4-amino-5,6-dichloro-2-pyrimidinyl)amino]benzonitrile (interm. 12).

Workup

  1. temperatureThe mixture was refluxed
  2. temperaturecooled
  3. filtrationfiltered
  4. customThe filtrate was evaporated
  5. dissolutionThe residue was dissolved in CH2Cl2
  6. washwashed with 1 N NaOH
  7. filtrationfiltered
  8. dissolutionThe solid was dissolved in 2-propanone
  9. customevaporated onto silica gel
  10. customchromatographed
  11. customThe pure fractions were collected
  12. customthe solvent was evaporated

Sources & evidence

ORD record
ord-52d15fc4d6fc4139af8d6f37a462d641
Source dataset
uspto-grants-2013_09
Patent number
US08530655B2

Reaction notes

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