N-(3-chloro-4-fluorophenyl)-N-(2-methyl-5-nitrophenyl)pyrimidine-4,6-diamine → N-(5-amino-2-methylphenyl)-N-(3-chloro-4-fluorophenyl)pyrimidine-4,6-diamine

HRID 2093492Notes

Reaction equation

HRID 2093492 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[CH:19][C:18]=2[CH3:26])[C:10]2[CH:15]=[C:14]([NH2:16])[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>CC(O)=O.CO.[Fe]>[NH2:23][C:21]1[CH:20]=[CH:19][C:18]([CH3:26])=[C:17]([N:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=2)[C:10]2[CH:15]=[C:14]([NH2:16])[N:13]=[CH:12][N:11]=2)[CH:22]=1

Participants

5

Reactant 1

HCID 66769443N-(3-chloro-4-fluorophenyl)-N-(2-methyl-5-nitrophenyl)pyrimidine-4,6-diamine

Product 1

HCID 66769431N-(5-amino-2-methylphenyl)-N-(3-chloro-4-fluorophenyl)pyrimidine-4,6-diamineYield 22.3%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

Synthesis of N-(5-Amino-2-methylphenyl)-N′-(3-chloro-4-fluorophenyl)-pyrimidine-4,6-diamine (Int-F) A mixture of 4-(3-chloro-4-fluorophenyl)-6-chloropyrimidin-4-ylamine (IR-4) (1.2 g, 4.6 mmol), 2-methyl-5-nitroaniline (0.85 g, 5.5 mmol) and 1 mL of concentrated HCl in 10 mL of n-butanol was heated at 120° C. for 16 h. With stifling, 5 mL of EtOAc was added to the reaction mixture. The light yellow colored product that precipitated was filtered and dried under vacuum to give N-(3-chloro-4-fluorophenyl)-N-(2-methyl-5-nitrophenyl)pyrimidine-4,6-diamine. MS (APCI) (m/z): 374/376 (M+1). A mixture of N-(3-chloro-4-fluorophenyl)-N-(2-methyl-5-nitrophenyl)pyrimidine-4,6-diamine (0.55 g, 1.5 mmol) and iron powder (35 mesh, 0.5 g, 5 eq) in 5 mL of HOAc and 2 mL of MeOH was heated at reflux for 2 h. The solvent was removed in vacuo and the dark colored residue was mixed with 150 mL of CH2Cl2 and 15 mL of sat. K2CO3 solution and was stirred at room temperature for 30 min. The organic layer was dried (MgSO4), was concentrated, and was then purified by flash chromatography (silica gel, MeOH/NH4OH/CH2Cl2) to afford 0.115 g of N-(5-amino-2-methylphenyl)-N-(3-chloro-4-fluorophenyl)pyrimidine-4,6-diamine as a light colored solid. (Int-F) MS (m/z): 344/346 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. customThe solvent was removed in vacuo
  4. additionthe dark colored residue was mixed with 150 mL of CH2Cl2 and 15 mL of sat. K2CO3 solution
  5. dry with materialThe organic layer was dried (MgSO4)
  6. concentrationwas concentrated
  7. customwas then purified by flash chromatography (silica gel, MeOH/NH4OH/CH2Cl2)

Sources & evidence

ORD record
ord-37be2955854042a7a6e21dcf27486996
Source dataset
uspto-grants-2013_05
Patent number
US08445498B2

Reaction notes

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