Diisopropylethylamine → 4-{3-[4-(Benzo[b]thiophen-2-yl)-5-methyl-pyrimidin-2-yl]-amino-propyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1986221Notes

Reaction equation

HRID 1986221 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][NH2:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[S:18]1[C:22]([C:23]2[C:28]([CH3:29])=[CH:27][N:26]=[C:25](Cl)[N:24]=2)=[CH:21][C:20]2[CH:31]=[CH:32][CH:33]=[CH:34][C:19]1=2.C(N(C(C)C)CC)(C)C>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][CH:16]([NH2:17])[C:25]2[N:24]=[C:23]([C:22]3[S:18][C:19]4[CH:34]=[CH:33][CH:32]=[CH:31][C:20]=4[CH:21]=3)[C:28]([CH3:29])=[CH:27][N:26]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 177509451-tert-Butyloxycarbonyl-4-(3-aminopropyl)piperazineHCID 866253634-(Benzo[b]thiophen-2-yl)-2-chloro-5-methyl-pyrimidine

Product 1

HCID 688562254-{3-[4-(Benzo[b]thiophen-2-yl)-5-methyl-pyrimidin-2-yl]-amino-propyl}-piperazine-1-carboxylic acid tert-butyl esterYield 70.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

4-(3-Aminopropyl)-piperazine-1-carboxylic acid tert-butyl ester (261 mg, 1.07 mmol) is added to a stirred suspension of 4-(benzo[b]thiophen-2-yl)-2-chloro-5-methyl-pyrimidine (140 mg, 0.537 mmol) and diisopropylethylamine (140 μL, 0.805 mmol) in anhydrous 1,4-dioxane (3.5 mL) at ambient temperature under nitrogen. The resultant mixture is heated in an oil bath at 95° C. for 36 hours. At ambient temperature the mixture is concentrated and chromatographed on silica gel, eluting with 2 M NH3/CH3OH in dichloromethane 0-6%, to give 4-{3-[4-(benzo[b]thiophen-2-yl)-5-methyl-pyrimidin-2-yl]-amino-propyl}-piperazine-1-carboxylic acid tert-butyl ester as a white solid (178 mg, 70% yield).

Workup

  1. concentrationAt ambient temperature the mixture is concentrated
  2. customchromatographed on silica gel
  3. washeluting with 2 M NH3/CH3OH in dichloromethane 0-6%

Sources & evidence

ORD record
ord-c54b43f900664a2c9aee2355974dad8d
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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