Diisopropylethylamine → {2-[5-Chloro-4-(4-cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-ethyl}-methylcarbamic acid tert-butyl ester

HRID 1986332Notes

Reaction equation

HRID 1986332 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[C:15]3[CH:14]=[C:13]([C:16]4[C:21]([Cl:22])=[CH:20][N:19]=[C:18](Cl)[N:17]=4)[S:12][C:11]=3[CH:10]=[CH:9][CH:8]=2)=[O:6])[CH2:3][CH2:2]1.[C:24]([O:28][C:29](=[O:35])[N:30]([CH2:32][CH2:33][NH2:34])[CH3:31])([CH3:27])([CH3:26])[CH3:25].C(N(C(C)C)CC)(C)C>O1CCOCC1>[C:24]([O:28][C:29](=[O:35])[N:30]([CH2:32][CH2:33][NH:34][C:18]1[N:17]=[C:16]([C:13]2[S:12][C:11]3[CH:10]=[CH:9][CH:8]=[C:7]([C:5](=[O:6])[NH:4][CH:1]4[CH2:3][CH2:2]4)[C:15]=3[CH:14]=2)[C:21]([Cl:22])=[CH:20][N:19]=1)[CH3:31])([CH3:27])([CH3:25])[CH3:26]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2756424N-Boc-N-methylethylenediamineHCID 866253512-(2,5-Dichloropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide

Product 1

HCID 68856879{2-[5-Chloro-4-(4-cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-ethyl}-methylcarbamic acid tert-butyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A stirred mixture of 2-(2,5-dichloropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide (406 mg, 1.12 mmol), (2-aminoethyl)-methylcarbamic acid tert-butyl ester (486 mg, 2.79 mmol) and diisopropylethylamine (432 mg, 3.34 mmol) in 1,4-dioxane (4 mL) is heated at 95° C. under nitrogen for 18 hours. 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 {2-[5-chloro-4-(4-cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-ethyl}-methylcarbamic acid tert-butyl ester as a foam (418 mg, 75% yield). The intermediate is then subjected to deprotection by dissolving this material (415 mg, 0.827 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 (352 mg, 90% yield). ES+(m/z) 402 (35Cl) and 404 (37Cl) [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-8778ca45078248dfb3102f6488d68bba
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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