p-Toluenesulfonic acid monohydrate → 2-(2-(2-(5-Methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)ethyl)phenyl)propanamide

HRID 592447Notes

Reaction equation

HRID 592447 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[CH:16]([CH3:20])[C:17]([NH2:19])=[O:18])[C:5]([CH3:21])=[CH:4][N:3]=1.[CH3:22][N:23]1[CH:27]=[C:26]([NH2:28])[CH:25]=[N:24]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[CH3:21][C:5]1[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH:16]([CH3:20])[C:17]([NH2:19])=[O:18])=[N:7][C:2]([NH:28][C:26]2[CH:25]=[N:24][N:23]([CH3:22])[CH:27]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 47709901-methyl-1H-pyrazol-4-amineHCID 867123232-(2-(2-(2-Chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)propanamide

Product 1

HCID 732949472-(2-(2-(5-Methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)ethyl)phenyl)propanamideYield 59%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)propanamide A49 (0.250 g, 0.823 mmol), 1-methyl-1H-pyrazol-4-amine (0.096 g, 0.99 mmol), and p-toluenesulfonic acid monohydrate (0.016 g, 0.082 mmol) in 1,4-dioxane (5 mL) was irradiated in the microwave at 120° C. for 3 hours. The volatiles were removed in vacuo and the residue was adsorbed onto silica and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 50-100% EtOAc in petroleum benzine 40-60° C., then 0-10% MeOH in EtOAc). The fractions containing suspected product were combined and the solvent removed in vacuo to give a green solid. The solid was adsorbed onto silica and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-10% MeOH in CHCl3) to give the title compound 51 as a white solid (0.178 g, 59%); 1H NMR (400 MHz, d6-DMSO) δ ppm 9.16 (s, 1H), 8.11 (s, 1H), 7.85 (s, 1H), 7.46 (s, 1H), 7.41-7.35 (m, 1H), 7.24 (s, 1H), 7.20-7.10 (m, 3H), 6.87 (s, 1H), 3.86 (q, J=7.1, 7.0, 7.0 Hz, 1H), 3.78 (s, 3H), 3.23-3.11 (m, 1H), 3.08-2.97 (m, 1H), 2.96-2.78 (m, 2H), 2.05 (s, 3H), 1.33 (d, J=6.9 Hz, 3H). LCMS-D: rt 2.99 min; m/z 365 [M+H]+.

Workup

  1. customwas irradiated in the microwave at 120° C. for 3 hours
  2. customThe volatiles were removed in vacuo
  3. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 50-100% EtOAc in petroleum benzine 40-60° C.
  4. additionThe fractions containing suspected product
  5. customthe solvent removed in vacuo
  6. customto give a green solid
  7. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-10% MeOH in CHCl3)

Sources & evidence

ORD record
ord-ce8cbe6b5dc044f1808f91843acf8cb3
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

Loading…