Water → N'-[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]-4-methoxy-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine

HRID 1842731노트

반응식

HRID 1842731 반응식
[Cl:1][C:2]1[C:3]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[NH:29][CH:28]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([N+:15]([O-])=O)[C:12]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[CH:11][C:10]=2[O:25][CH3:26])=[N:6][CH:7]=1.[NH4+].[Cl-].O.C(Cl)Cl>C(O)C.[Fe].CO>[Cl:1][C:2]1[C:3]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[NH:29][CH:28]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([NH2:15])[C:12]([N:18]3[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]3)=[CH:11][C:10]=2[O:25][CH3:26])=[N:6][CH:7]=1

참가 물질

8

반응물 4

HCID 962WaterHCID 6344DichloromethaneHCID 25517Ammonium ChlorideHCID 712408115-chloro-4-(1H-indol-3-yl)-N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]pyrimidin-2-amine2회

생성물 1

HCID 73292722N'-[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]-4-methoxy-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine수율 88%

시약·촉매·용매 3

HCID 23925Iron촉매HCID 702Ethanol용매HCID 887Methanol용매

실험 절차

A mixture of 5-chloro-4-(1H-indol-3-yl)-N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]pyrimidin-2-amine (Intermediate 75, 350 mg, 0.71 mmol), iron (237 mg, 4.25 mmol) and NH4Cl (26.5 mg, 0.50 mmol) were heated at reflux in ethanol (24 mL) and water (8 mL) for 2 h. The mixture was then cooled and concentrated in vacuo to give a thick slurry. CH2Cl2 (100 mL) and CH3OH (10 mL) were added and the mixture was stirred for 0.25 h and then filtered. The filter cake was washed with further CH2Cl2 and CH3OH, and the combined organics were dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1-5% methanolic ammonia in CH2Cl2 gave the title compound (288 mg, 88%) as a yellow dry film; 1H NMR: 2.26 (3H, s), 2.47-2.56 (4H, m), 2.88 (4H, t), 3.70 (3H, s), 4.29 (2H, d), 6.72 (1H, s), 7.04 (1H, t), 7.14 (1H, s), 7.15-7.22 (1H, m), 7.46 (1H, d), 8.18 (1H, s), 8.35 (2H, d), 8.48 (1H, d), 11.81 (1H, s); m/z: ES+ MH+ 464.49.

후처리

  1. temperaturewere heated
  2. temperatureThe mixture was then cooled
  3. concentrationconcentrated in vacuo
  4. customto give a thick slurry
  5. filtrationfiltered
  6. washThe filter cake was washed with further CH2Cl2 and CH3OH
  7. dry with materialthe combined organics were dried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification by FCC
  10. washeluting with 1-5% methanolic ammonia in CH2Cl2

출처 및 근거

ORD 기록
ord-f1af6e9f229e46e9a1f7aca64a4bdfb5
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

반응 노트

불러오는 중…