Ammonium Chloride → Mutated EGFR-IN-1

HRID 1842754ノート

反応式

HRID 1842754 の反応式
[CH3:1][N:2]([CH3:35])[CH2:3][CH2:4][N:5]([CH3:34])[C:6]1[C:11]([N+:12]([O-])=O)=[CH:10][C:9]([NH:15][C:16]2[N:21]=[C:20]([C:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[N:24]([CH3:31])[CH:23]=3)[CH:19]=[CH:18][N:17]=2)=[C:8]([O:32][CH3:33])[CH:7]=1.[NH4+].[Cl-]>C(O)C.O.[Fe]>[CH3:35][N:2]([CH3:1])[CH2:3][CH2:4][N:5]([CH3:34])[C:6]1[C:11]([NH2:12])=[CH:10][C:9]([NH:15][C:16]2[N:21]=[C:20]([C:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[N:24]([CH3:31])[CH:23]=3)[CH:19]=[CH:18][N:17]=2)=[C:8]([O:32][CH3:33])[CH:7]=1

参加物

6

反応物 2

HCID 25517Ammonium ChlorideHCID 71239349N1-(2-(Dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl)-2-nitro-1,4-benzenediamine2 回

生成物 1

HCID 78358313Mutated EGFR-IN-1収率 85.4%

試薬・触媒・溶媒 3

HCID 23925Iron触媒HCID 702Ethanol溶媒HCID 962Water溶媒

実験手順

A mixture of N′-(2-dimethylaminoethyl)-2-methoxy-N′-methyl-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]-5-nitrobenzene-1,4-diamine (Intermediate 101, 220 mg, 0.46 mmol), iron (155 mg, 2.78 mmol) and NH4Cl (17.32 mg, 0.32 mmol) in ethanol (12 mL) and water (4 mL) was heated at reflux for 2 h. The crude mixture was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M methanolic ammonia and appropriate fractions were combined and concentrated in vacuo onto silica. Purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (175 mg, 85%) as a beige foam; 1H NMR: 2.17 (6H, s), 2.36 (2H, t), 2.63 (3H, s), 2.88 (2H, t), 3.74 (3H, s), 3.88 (3H, s), 4.58 (2H, br s), 6.76 (1H, s), 7.12-7.19 (2H, m), 7.21-7.27 (1H, m), 7.48 (1H, s), 7.51 (1H, d), 7.78 (1H, s), 8.27 (1H, d), 8.30 (1H, s), 8.42 (1H, d); m/z: ES+ MH+ 446.32.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. customThe crude mixture was purified by ion exchange chromatography
  4. washThe desired product was eluted from the column
  5. concentrationconcentrated in vacuo onto silica
  6. customPurification by FCC
  7. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2

出典と根拠

ORDレコード
ord-0d3b14c7ba2b4ec4a14984501ac774e8
出典データセット
uspto-grants-2015_02
特許番号
US08946235B2

反応ノート

読み込み中…