Ammonium Chloride → N4-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-5-methoxy-N1-methyl-N1-[2-(4-methylpiperazin-1-yl)ethyl]benzene-1,2,4-triamine

HRID 1842761Notes

Reaction equation

HRID 1842761 reaction equation
[Cl:1][C:2]1[C:3]([C:31]2[CH:32]=[N:33][N:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=23)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([N+:15]([O-])=O)[C:12]([N:18]([CH3:28])[CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)=[CH:11][C:10]=2[O:29][CH3:30])=[N:6][CH:7]=1.[NH4+].[Cl-]>CCO.O.[Fe]>[Cl:1][C:2]1[C:3]([C:31]2[CH:32]=[N:33][N:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=23)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([NH2:15])[C:12]([N:18]([CH3:28])[CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)=[CH:11][C:10]=2[O:29][CH3:30])=[N:6][CH:7]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 71240746N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-2-methoxy-N'-methyl-N'-(2-(4-methylpiperazin-1-yl)ethyl]-5-nitrobenzene-1,4-diamine

Product 1

HCID 86677275N4-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-5-methoxy-N1-methyl-N1-[2-(4-methylpiperazin-1-yl)ethyl]benzene-1,2,4-triamineYield 94%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-2-methoxy-N′-methyl-N′-[2-(4-methylpiperazin-1-yl)ethyl]-5-nitrobenzene-1,4-diamine (0.182 g, 0.33 mmol), iron (0.110 g, 1.98 mmol) and NH4Cl (0.012 g, 0.23 mmol) in EtOH (10 mL) and water (3.33 mL) was heated at reflux for 1.5 h. The mixture was then cooled to r.t., filtered and concentrated in vacuo. Purification by ion exchange chromatography, using an SCX column and eluting with 1M methanolic ammonia provided a brown gum (162 mg) after concentration of appropriate fractions. Further purification by FCC, eluting with 2-7% 1M methanolic ammonia in CH2Cl2 gave the title compound (0.148 g, 86%) as a yellow gum; 1H NMR: (CDCl3) 2.28 (3H, s), 2.32-2.63 (10H, m), 2.70 (3H, s), 2.98 (2H, t), 3.84 (3H, s), 4.05 (2H, d), 6.71 (1H, s), 6.95 (1H, td), 7.38 (1H, ddd), 7.52 (1H, d), 7.88 (1H, s), 8.36 (1H, s), 8.57 (1H, d), 8.65 (1H, d), 8.93 (1H, s); m/z: ES+ MH+ 522.57.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1.5 h
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by ion exchange chromatography
  6. washeluting with 1M methanolic ammonia

Sources & evidence

ORD record
ord-77a3ae171f75453eb2ee37c6fe255593
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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