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 577308노트

반응식

HRID 577308 반응식
[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

참가 물질

5

반응물 1

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

생성물 1

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

시약·촉매·용매 3

HCID 23925Iron촉매HCID 176Acetic Acid용매HCID 887Methanol용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-36a0841547de4eba8ddcf0ae808a37ba
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040541B2

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