Water → 1-(2-(2-(5-chloro-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592393Notes

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.O.[CH3:24][N:25]1[CH2:30][CH2:29][CH:28]([N:31]2[CH:35]=[C:34]([NH2:36])[CH:33]=[N:32]2)[CH2:27][CH2:26]1>CO>[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:36][C:34]2[CH:33]=[N:32][N:31]([CH:28]3[CH2:29][CH2:30][N:25]([CH3:24])[CH2:26][CH2:27]3)[CH:35]=2)=[N:3][CH:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A14 (0.060 g, 0.21 mmol) in MeOH (1.0 mL) and water (0.1 mL) containing 1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-amine (0.039 g, 0.21 mmol) was heated at 70° C. for 48 hours. The mixture was adsorbed onto silica gel and purified by silica column chromatography (Combiflash Rf, 4 g SiO2 Cartridge, 0-50% MeOH in DCM). Further purification by HPLC (eluting with 30-100% gradient in acetonitrile containing 0.1% formic acid and water containing 0.1% formic acid, flow rate 4.0 mL/min) gave the title compound 18 as a light yellow solid (0.015 g, 17%). LCMS-C: rt 4.31 min; m/z 480 [M+H]+.

Workup

custompurified by silica column chromatography (Combiflash Rf, 4 g SiO2 Cartridge, 0-50% MeOH in DCM)
customFurther purification
washby HPLC (eluting with 30-100% gradient in acetonitrile containing 0.1% formic acid and water containing 0.1% formic acid, flow rate 4.0 mL/min)

Sources & evidence

ORD record: ord-72c40067622a4f7ba5ef2f64ffc37d70
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238644B2

Reaction notes

Loading…