Ammonium Chloride → N'-[5-chloro-4-(1-methylindol-3-yl)pyrimidin-2-yl]-4-methoxy-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine

HRID 1842747ノート

反応式

HRID 1842747 の反応式
[Cl:1][C:2]1[C:3]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]([CH3:36])[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-]>C(O)C.O.[Fe]>[Cl:1][C:2]1[C:3]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]([CH3:36])[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

参加物

6

反応物 2

HCID 25517Ammonium ChlorideHCID 712408915-chloro-N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine2 回

生成物 1

HCID 86677339N'-[5-chloro-4-(1-methylindol-3-yl)pyrimidin-2-yl]-4-methoxy-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine収率 52%

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 5-chloro-N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 92, 750 mg, 1.48 mmol), iron (495 mg, 8.86 mmol) and NH4Cl (55.3 mg, 1.03 mmol) in ethanol (12 mL) and water (4 mL) was heated at reflux for 4 h. Purification by ion exchange chromatography, using an SCX column and eluting with 7M methanolic ammonia provided part-purified material that was concentrated in vacuo onto silica. Purification by FCC, eluting with 0-4% 7N methanolic ammonia in CH2Cl2 gave the title compound (367 mg, 52%) as a yellow solid. Impure fractions containing desired product were concentrated in vacuo and the resulting residue was triturated with CH2Cl2/diethyl ether to give more of the title compound (230 mg, 33%) as a yellow solid. Total: 597 mg, 85%; 1H NMR: (CDCl3) 2.37 (3H, s), 2.56 (4H, br s), 2.95 (4H, br t), 3.75 (2H, br s), 3.84 (3H, s), 3.90 (3H, s), 6.70 (1H, s), 7.27-7.36 (2H, m), 7.38-7.42 (1H, m), 7.63 (1H, s), 8.13 (1H, s), 8.21 (1H, s), 8.33 (1H, s), 8.63-8.69 (1H, m); m/z: ES+ MH+ 478.55.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 4 h
  3. customPurification by ion exchange chromatography
  4. washeluting with 7M methanolic ammonia
  5. customprovided
  6. custompart-purified material that
  7. concentrationwas concentrated in vacuo onto silica
  8. customPurification by FCC
  9. washeluting with 0-4% 7N methanolic ammonia in CH2Cl2

出典と根拠

ORDレコード
ord-469bec4854764b4191983991330ca7c9
出典データセット
uspto-grants-2015_02
特許番号
US08946235B2

反応ノート

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