Isopropanol → (R)-[3-amino-4-[[1-(hydroxymethyl)-3-methylbutyl]amino]phenyl][4-amino-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-5-thiazolyl]methanone

HRID 10811Notes

Reaction equation

HRID 10811 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([N:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)=[CH:29][CH:28]=2)[S:5][C:6]=1[C:7]([C:9]1[CH:14]=[CH:13][C:12]([NH:15][C@@H:16]([CH2:21][OH:22])[CH2:17][CH:18]([CH3:20])[CH3:19])=[C:11]([N+:23]([O-])=O)[CH:10]=1)=[O:8].NN.CC(O)C>[Pd].ClCCl.CO>[NH2:23][C:11]1[CH:10]=[C:9]([C:7]([C:6]2[S:5][C:4]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([N:33]4[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]4)=[CH:29][CH:28]=3)=[N:3][C:2]=2[NH2:1])=[O:8])[CH:14]=[CH:13][C:12]=1[NH:15][C@@H:16]([CH2:21][OH:22])[CH2:17][CH:18]([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 3776IsopropanolHCID 9321HydrazineHCID 60092052(R)-[4-Amino-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-5-thiazolyl][3-nitro-4-[[1-(hydroxymethyl)-3-methylbutyl]amino]phenyl]methanone

Product 1

HCID 60092054(R)-[3-amino-4-[[1-(hydroxymethyl)-3-methylbutyl]amino]phenyl][4-amino-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-5-thiazolyl]methanoneYield 57.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of (R)-[4-amino-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-5-thiazolyl][3-nitro-4-[[1-(hydroxymethyl)-3-methylbutyl]amino]phenyl]methanone (of Example 63; 30 mg, 0.05 mmol), NH2NH2 (0.5 mL), 10% Pd/C (5 mg), and 2-propanol (2 mL) was heated at reflux for 1 h. The mixture was filtered through a Celite™ pad and concentrated in vacuo. Flash chromatography with 4:1 dichloromethane/methanol furnished (R)-[3-amino-4-[[1-(hydroxymethyl)-3-methylbutyl]amino]phenyl][4-amino-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-5-thiazolyl]methanone (15 mg, 53% yield).

Workup

  1. temperatureat reflux for 1 h
  2. filtrationThe mixture was filtered through a Celite™ pad
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e22344accb1d4910a848b743bfa211d1
Source dataset
uspto-grants-2006_08
Patent number
US07094896B2

Reaction notes

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