Methylamine → p38alpha Inhibitor 2

HRID 2070860Notes

Reaction equation

HRID 2070860 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

4

Reactant 2

HCID 6329MethylamineHCID 666886643-[3-[[1-[2-(2-Chloroethoxy)phenyl]-1-methylethyl]amino]-2-oxo-1(2H)-pyrazinyl]-N-cyclopropyl-4-methyl-benzamide

Product 1

HCID 25145735p38alpha Inhibitor 2

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

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

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

Sources & evidence

ORD record
ord-f50df4c905b949359bf5689747db3fb3
Source dataset
uspto-grants-2012_10
Patent number
US08299246B2

Reaction notes

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