4-Chloro-N-methylbenzenamine → HCID 90289979、化合物

HRID 1471654ノート

反応式

HRID 1471654 の反応式
ClC(Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[Br:13][C:14]1[CH:15]=[C:16]([CH:27]=[C:28]([F:30])[CH:29]=1)[CH2:17][NH:18][NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].[CH:31]([N:34]([CH2:38]C)[CH:35]([CH3:37])[CH3:36])(C)C.[Cl:40][C:41]1[CH:48]=CC(NC)=C[CH:42]=1>C(Cl)Cl>[Br:13][C:14]1[CH:15]=[C:16]([CH:27]=[C:28]([F:30])[CH:29]=1)[CH2:17][N:18]([C:38](=[O:4])[N:34]([C:35]1[CH:36]=[CH:48][C:41]([Cl:40])=[CH:42][CH:37]=1)[CH3:31])[NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21]

参加物

6

反応物 4

HCID 702724-Chloro-N-methylbenzenamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 90280216HCID 90280216、化合物

生成物 1

HCID 90289979HCID 90289979、化合物収率 37%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒4 回

反応条件

温度
0 °C

実験手順

Triphosgene (593 mg, 2.0 mmol) was dissolved in 13 mL of methylene chloride and cooled to 0° C. To it was added a solution of tert-butyl 2-(3-bromo-5-fluorobenzyl)hydrazinecarboxylate (1.6 g, 5 mmol) and N,N-diisopropylethylamine (1.3 mL, 7.5 mmol) in 13 mL of methylene chloride. The reaction mixture was allowed to stir at 0° C. for 20 min, and to it was added a solution of 4-chloro-N-methylaniline (726 μL, 6 mmol) in 4 mL of methylene chloride. The resulting mixture was allowed to stir at ambient temperature for 3 days. It was diluted with methylene chloride and washed with 1N HCl, half saturated NaHCO3 and half brine, then dried over MgSO4, filtered and concentrated. The residue was purified by silica gel chromatography eluting with ethyl acetate and hexanes to afford 359 mg of tert-butyl 2-(3-bromo-5-fluorobenzyl)-2-((4-chlorophenyl)(methyl)carbamoyl)hydrazinecarboxylate (0.74 mmol). It was then dissolved in 2 mL of methanol, and to it was added 4N HCl in 1,4-dioxane (0.9 mL, 3.7 mmol). The mixture was stirred at ambient temperature overnight. The solvent was removed to afford 1-(3-bromo-5-fluorobenzyl)-N-(4-chlorophenyl)-N-methylhydrazinecarboxamide hydrochloride. MS (m/z): 387.9 [M+H]+; HPLC retention time 3.88 min (5-99% acetonitrile:water with 0.05% formic acid).

後処理

  1. stirringto stir at ambient temperature for 3 days
  2. washwashed with 1N HCl, half saturated NaHCO3 and half brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with ethyl acetate and hexanes

出典と根拠

ORDレコード
ord-fc0cdc59f5fd478ba7c661b7664a32aa
出典データセット
uspto-grants-2015_04
特許番号
US09012441B2

反応ノート

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