Hydrochloric Acid → N-(3-chloro-4-fluorophenyl)-N'-(2-methyl-5-nitrophenyl)pyrimidine-4,6-diamine

HRID 1014101Notes

Reaction equation

HRID 1014101 reaction equation
NC1C=CC(C)=C(N[C:9]2[CH:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=3)[N:12]=[CH:11][N:10]=2)C=1.ClC1C=C(C2(N)C=C(Cl)N=CN2)C=CC=1F.[CH3:41][C:42]1[CH:48]=[CH:47][C:46]([N+:49]([O-:51])=[O:50])=[CH:45][C:43]=1[NH2:44].Cl>C(O)CCC.CCOC(C)=O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:13]2[CH:14]=[C:9]([NH:44][C:43]3[CH:45]=[C:46]([N+:49]([O-:51])=[O:50])[CH:47]=[CH:48][C:42]=3[CH3:41])[N:10]=[CH:11][N:12]=2)[CH:21]=[CH:20][C:19]=1[F:22]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 74442-Methyl-5-NitroanilineHCID 67316172N-(5-amino-2-methylphenyl)-N'-(3-chloro-4-fluorophenyl)pyrimidine-4,6-diamineHCID 178507140HCID 178507140, compound

Product 1

HCID 67316315N-(3-chloro-4-fluorophenyl)-N'-(2-methyl-5-nitrophenyl)pyrimidine-4,6-diamine

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

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 stirring, 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. customThe light yellow colored product that precipitated
  2. filtrationwas filtered
  3. customdried under vacuum

Sources & evidence

ORD record
ord-b117ea9ae2d743c9916a022997e9f748
Source dataset
uspto-grants-2011_07
Patent number
US07982036B2

Reaction notes

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