Diisopropylethylamine → 4-{3-[4-(4-Cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-5-fluoropyrimidin-2-ylamino]-propyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1986268Notes

Reaction equation

HRID 1986268 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][CH2:16][NH2:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:18]1([NH:21][C:22]([C:24]2[C:32]3[CH:31]=[C:30]([C:33]4[C:38]([F:39])=[CH:37][N:36]=[C:35](Cl)[N:34]=4)[S:29][C:28]=3[CH:27]=[CH:26][CH:25]=2)=[O:23])[CH2:20][CH2:19]1.C(N(C(C)C)CC)(C)C>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][CH2:16][NH:17][C:35]2[N:34]=[C:33]([C:30]3[S:29][C:28]4[CH:27]=[CH:26][CH:25]=[C:24]([C:22](=[O:23])[NH:21][CH:18]5[CH2:19][CH2:20]5)[C:32]=4[CH:31]=3)[C:38]([F:39])=[CH:37][N:36]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 22990164tert-Butyl 4-(3-aminopropyl)piperidine-1-carboxylateHCID 866253762-(2-Chloro-5-fluoropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide

Product 1

HCID 689062074-{3-[4-(4-Cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-5-fluoropyrimidin-2-ylamino]-propyl}-piperidine-1-carboxylic acid tert-butyl esterYield 80.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

4-(3-Aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester (0.557 g, 2.30 mmol) is added to a stirred suspension of 2-(2-chloro-5-fluoropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide (0.400 g, 1.15 mmol) and diisopropylethylamine (0.60 mL, 3.5 mmol) in anhydrous 1,4-dioxane (8 mL) at room temperature under nitrogen. The resultant mixture is heated in an oil bath at 95° C. for 34 hours. At room temperature the mixture is concentrated and chromatographed on silica gel, eluting with CH3OH in dichloromethane: 0-2%, to give 4-{3-[4-(4-cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-5-fluoropyrimidin-2-ylamino]-propyl}-piperidine-1-carboxylic acid tert-butyl ester (0.512 g) as a solid.

Workup

  1. concentrationAt room temperature the mixture is concentrated
  2. customchromatographed on silica gel
  3. washeluting with CH3OH in dichloromethane

Sources & evidence

ORD record
ord-c40b848a7ad741dba88aab3d27ff2c44
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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