p-Toluenesulfonic acid → 1-(2-(2-(5-Chloro-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592386Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([Cl:22])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[Cl:22][C:5]1[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)=[N:7][C:2]([NH:23][C:24]2[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=2)=[N:3][CH:4]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A14 (1.50 g, 4.46 mmol) in 1,4-dioxane (25 mL) containing 4-amino-1-methylpyrazole (0.520 g, 5.35 mmol) and p-toluenesulfonic acid (0.085 g, 0.45 mmol) was heated under microwave irradiation at 120° C. for 7 hours. The volatiles were removed in vacuo and the residue was adsorbed onto silica gel and the product was separated using silica column chromatography (Combiflash Rf, 40 g SiO2 Cartridge, 60-100% EtOAc in cyclohexane and then 0-5% MeOH in DCM) to give the title compound 13 as a light orange foam (1.01 g, 56%). 1H NMR (300 MHz, d6-DMSO) δ 9.64 (s, 1H), 8.37 (s, 1H), 7.87 (s, 1H), 7.46 (s, 1H), 7.22-7.36 (m, 4H), 7.00 (brs, 1H), 6.01 (brs, 1H), 3.81 (s, 3H), 3.09 (brs, 4H), 1.45-1.44 (m, 2H), 1.00-0.99 (m, 2H). LCMS-B: rt 6.318 min; m/z 397 [M+H]+.

Workup

customThe volatiles were removed in vacuo
customthe product was separated

Sources & evidence

ORD record: ord-daac9150421443a59eabae0f8662a31b
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238644B2

Reaction notes

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