1-(3-Aminopropyl)-4-methylpiperazine → 2-{5-Methyl-2-[3-(4-methylpiperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophene-4-carboxylic acid methylamide tri-hydrochloride

HRID 1986340Notes

Reaction equation

[CH3:1][NH:2][C:3]([C:5]1[C:13]2[CH:12]=[C:11]([C:14]3[C:19]([CH3:20])=[CH:18][N:17]=[C:16]([Cl:21])[N:15]=3)[S:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4].[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][CH2:31][NH2:32])[CH2:25][CH2:24]1>O1CCOCC1>[ClH:21].[ClH:21].[ClH:21].[CH3:1][NH:2][C:3]([C:5]1[C:13]2[CH:12]=[C:11]([C:14]3[C:19]([CH3:20])=[CH:18][N:17]=[C:16]([NH:32][CH2:31][CH2:30][CH2:29][N:26]4[CH2:25][CH2:24][N:23]([CH3:22])[CH2:28][CH2:27]4)[N:15]=3)[S:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4]

Participants

Conditions

Temperature: 95 °C

Procedure

A stirred mixture of 2-(2-chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid methylamide (400 mg, 1.26 mmol) and 3-(4-methylpiperazin-1-yl)-propylamine (594 mg, 3.78 mmol) in 1,4-dioxane (6 mL) is heated at 95° C. under a nitrogen atmosphere for 60 hours. After concentration and subsequent chromatography on silica gel, eluting with 2 M NH3/MeOH in dichloromethane 0-8%, the free base of the title compound is obtained as a solid (325 mg, 59% yield). The free base (300 mg, 0.684 mmol) is dissolved in MeOH (20 mL) and dichloromethane (20 mL) and the solution is bubbled with a small stream of anhydrous HCl gas for 2 minutes. After concentration, the solid is suspended in MeOH (5 mL) and diethyl ether (20 mL), sonicated, filtered and dried at 60° C. under vacuum to give the title compound as a yellow solid (311 mg, 83% yield). ES+(m/z) 439 [M(free base)+H].

Workup

concentrationAfter concentration and subsequent chromatography on silica gel
washeluting with 2 M NH3/MeOH in dichloromethane 0-8%

Sources & evidence

ORD record: ord-96240fe7c6a246a3aff34177bf82ea8d
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07547691B2

Reaction notes

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