Ammonium Chloride → N-[5-chloro-4-(1-methylindol-3-yl)pyrimidin-2-yl]-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamine

HRID 1842766ノート

反応式

HRID 1842766 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[CH2:21][CH:20]([N:22]([CH3:24])[CH3:23])[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[C:10]([O:25][CH3:26])=[CH:11][C:12]([N:18]3[CH2:19][CH:20]([N:22]([CH3:24])[CH3:23])[CH2:21]3)=[C:13]([NH2:15])[CH:14]=2)=[N:6][CH:7]=1

参加物

6

反応物 2

HCID 25517Ammonium ChlorideHCID 712408245-chloro-N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine2 回

生成物 1

HCID 86677279N-[5-chloro-4-(1-methylindol-3-yl)pyrimidin-2-yl]-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamine収率 98.3%

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-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 113, 285 mg, 0.56 mmol), iron (188 mg, 3.37 mmol) and NH4Cl (22.51 mg, 0.42 mmol) in ethanol (9 mL) and water (3 mL) was heated at reflux for 2 h. The mixture was then cooled and filtered through diatomaceous earth (Celite™). The filtrate was concentrated in vacuo and the resulting residue was dissolved in CH2Cl2. This solution was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1-20% 7N methanolic ammonia in CH2Cl2 gave the title compound (263 mg, 98%) as a brown dry film; 1H NMR: (CDCl3) 2.21 (6H, s), 3.08-3.18 (1H, m), 3.30 (2H, br s), 3.58 (2H, t), 3.86 (3H, s), 3.88 (3H, s), 3.93 (2H, t), 6.38 (1H, s), 7.2-7.42 (3H, m, partially obscured by chloroform signal), 7.50 (1H, s), 7.99 (1H, s), 8.20 (1H, s), 8.31 (1H, s), 8.63 (1H, d); m/z: ES+ MH+ 478.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. temperatureThe mixture was then cooled
  4. filtrationfiltered through diatomaceous earth (Celite™)
  5. concentrationThe filtrate was concentrated in vacuo
  6. dissolutionthe resulting residue was dissolved in CH2Cl2
  7. washThis solution was washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customPurification by FCC
  11. washeluting with 1-20% 7N methanolic ammonia in CH2Cl2

出典と根拠

ORDレコード
ord-f91bbf22da9d49de87bf2328480abea4
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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