Diisopropylethylamine → 4-{2-[5-Methyl-4-(6-methylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1986334Notes

Reaction equation

HRID 1986334 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]2[CH:12]=[C:11]([C:13]3[C:18]([CH3:19])=[CH:17][N:16]=[C:15](Cl)[N:14]=3)[S:10][C:9]=2[CH:21]=1)=[O:4].[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([CH2:35][CH2:36][NH2:37])[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(N(C(C)C)CC)(C)C>O1CCOCC1>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([CH2:35][CH2:36][NH:37][C:15]2[N:14]=[C:13]([C:11]3[S:10][C:9]4[CH:21]=[C:5]([C:3](=[O:4])[NH:2][CH3:1])[CH:6]=[CH:7][C:8]=4[CH:12]=3)[C:18]([CH3:19])=[CH:17][N:16]=2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1514258tert-Butyl 4-(2-aminoethyl)piperidine-1-carboxylateHCID 866253852-(2-Chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-6-carboxylic acid methylamide

Product 1

HCID 688579074-{2-[5-Methyl-4-(6-methylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-ethyl}-piperidine-1-carboxylic acid tert-butyl esterYield 43.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A stirred mixture of 2-(2-chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-6-carboxylic acid methylamide (400 mg, 1.20 mmol), 4-(2-aminoethyl)-piperidine-1-carboxylic acid tert-butyl ester (688 mg, 3.01 mmol) and diisopropylethylamine (467 mg, 3.61 mmol) in 1,4-dioxane (4 mL) is heated at 95° C. under nitrogen for 3 days. At room temperature the mixture is concentrated and the crude product is chromatographed on silica gel, eluting with EtOAc in dichloromethane 0-35%, to give 4-{2-[5-methyl-4-(6-methylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester as a solid (264 mg, 43% yield). The intermediate is subjected to deprotection by dissolving this material (264 mg, 0.518 mmol) in MeOH (12 mL) and bubbling anhydrous HCl gas for 5 minutes. The hot, yellow solution is allowed to sit at room temperature for 2 hours, then concentrated to give the title compound as a yellow solid (246 mg, 98% yield). ES+(m/z) 410 [M(free base)+H].

Workup

  1. concentrationAt room temperature the mixture is concentrated
  2. customthe crude product is chromatographed on silica gel
  3. washeluting with EtOAc in dichloromethane 0-35%

Sources & evidence

ORD record
ord-d89437bb967f4732826738756fbf5cb2
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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