Ammonium Chloride → Mutated EGFR-IN-1

HRID 1842754

반응식

HRID 1842754 반응식
[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

참가 물질

6

반응물 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-benzenediamine2회

생성물 1

HCID 78358313Mutated EGFR-IN-1수율 85.4%

시약·촉매·용매 3

HCID 23925Iron촉매HCID 702Ethanol용매HCID 962Water용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0d3b14c7ba2b4ec4a14984501ac774e8
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

연결된 노트

불러오는 중…