Methylamine → p38alpha Inhibitor 2

HRID 337180Notes

Reaction equation

Cl[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]([NH:14][C:15]1[C:16](=[O:34])[N:17]([C:21]2[CH:22]=[C:23]([CH:30]=[CH:31][C:32]=2[CH3:33])[C:24]([NH:26][CH:27]2[CH2:29][CH2:28]2)=[O:25])[CH:18]=[CH:19][N:20]=1)([CH3:13])[CH3:12].[CH3:35][NH2:36]>O1CCOCC1>[CH:27]1([NH:26][C:24](=[O:25])[C:23]2[CH:30]=[CH:31][C:32]([CH3:33])=[C:21]([N:17]3[CH:18]=[CH:19][N:20]=[C:15]([NH:14][C:11]([CH3:13])([C:6]4[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=4[O:4][CH2:3][CH2:2][NH:36][CH3:35])[CH3:12])[C:16]3=[O:34])[CH:22]=2)[CH2:29][CH2:28]1

Participants

Conditions

Temperature: 100 °C

Procedure

3-[3-[[1-[2-(2-Chloroethoxy)phenyl]-1-methylethyl]amino]-2-oxo-1(2H)-pyrazinyl]-N-cyclopropyl-4-methyl-benzamide (Example 198e, 17.5 g) in dioxane (50 mL) was treated with 40% Methylamine solution (50 mL) under nitrogen. The resulting suspension was heated in a sealed system at 100° C. for 4 h. After cooling to room temperature, the solution was evaporated to dryness. The crude product was purified by flash chromatography (SiO2, eluent 10% methanol in dichloromethane and 1% triethylamine). Evaporation of the relevant fractions to dryness and trituration of the residue in diethyl ether gave a solid which was filtered off and dried to give the title compound (12.5 g) as an off white solid.

Workup

temperatureAfter cooling to room temperature
customthe solution was evaporated to dryness
customThe crude product was purified by flash chromatography (SiO2, eluent 10% methanol in dichloromethane and 1% triethylamine)
customEvaporation of the relevant fractions to dryness and trituration of the residue in diethyl ether
customgave a solid which
filtrationwas filtered off
customdried

Sources & evidence

ORD record: ord-3aeefc8f72914c6ba88b79be3aefd8c3
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889692B2

Reaction notes

Loading…