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

HRID 592409Notes

Reaction equation

[CH:1]([N:4]1[CH:8]=[C:7]([NH2:9])[CH:6]=[N:5]1)([CH3:3])[CH3:2].Cl[C:11]1[N:16]=[C:15]([CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]2([C:28]([NH2:30])=[O:29])[CH2:27][CH2:26]2)[C:14]([Cl:31])=[CH:13][N:12]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O>O1CCOCC1>[Cl:31][C:14]1[C:15]([CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]2([C:28]([NH2:30])=[O:29])[CH2:27][CH2:26]2)=[N:16][C:11]([NH:9][C:7]2[CH:6]=[N:5][N:4]([CH:1]([CH3:3])[CH3:2])[CH:8]=2)=[N:12][CH:13]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 1-isopropylpyrazol-4-amine (0.083 g, 0.66 mmol), 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A14 (0.110 g, 0.327 mmol) and TsOH.H2O (0.013 g, 0.066 mmol) in 1,4-dioxane (2.0 mL) was heated in the microwave to 100° C. for 3 hours. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography (0-100% EtOAc in petroleum benzine 40-60° C. then 0-10% MeOH in EtOAc) to give the title compound 30 (0.094 g, 68%). LCMS-D: rt 3.355 min; m/z 425.3 [M+H]+.

Workup

concentrationThe mixture was concentrated under reduced pressure
custompurified by silica gel column chromatography (0-100% EtOAc in petroleum benzine 40-60° C.

Sources & evidence

ORD record: ord-eb10be310a714066af1215c929ba0612
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238644B2

Reaction notes

Loading…