Diisopropylethylamine → 6-Ethyl-3-{[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]amino}-5-(3-nitrophenoxy)pyrazine-2-carboxamide

HRID 1526165Notes

Reaction equation

HRID 1526165 reaction equation
Cl[C:2]1[C:3]([C:20]([NH2:22])=[O:21])=[N:4][C:5]([CH2:18][CH3:19])=[C:6]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[N:7]=1.[CH3:23][N:24]1[CH2:29][CH2:28][N:27]([C:30]2[N:35]=[CH:34][C:33]([NH2:36])=[CH:32][N:31]=2)[CH2:26][CH2:25]1.C(N(C(C)C)CC)(C)C>CN1CCCC1=O.C(OCC)(=O)C>[CH2:18]([C:5]1[N:4]=[C:3]([C:20]([NH2:22])=[O:21])[C:2]([NH:36][C:33]2[CH:32]=[N:31][C:30]([N:27]3[CH2:28][CH2:29][N:24]([CH3:23])[CH2:25][CH2:26]3)=[N:35][CH:34]=2)=[N:7][C:6]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=1)[CH3:19]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 568284122-(4-Methylpiperazin-1-yl)pyrimidin-5-amineHCID 897091113-Chloro-6-ethyl-5-(3-nitrophenoxy)pyrazine-2-carboxamide

Product 1

HCID 1176670526-Ethyl-3-{[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]amino}-5-(3-nitrophenoxy)pyrazine-2-carboxamideYield 52.5%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-chloro-6-ethyl-5-(3-nitrophenoxy)pyrazine-2-carboxamide (300 mg), 2-(4-methylpiperazin-1-yl)pyrimidine-5-amine (198 mg), and diisopropylethylamine (318 μL) in N-methylpyrrolidone (1.5 mL) was heated at 120° C. for 18 hours. The reaction mixture was cooled, and then diluted with ethyl acetate, and the organic phase was washed with water and saturated brine. After drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous anunonia=1:0:0-95:4.5:0.5) to obtain 6-ethyl-3-{[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]amino}-5-(3-nitrophenoxy)pyrazine-2-carboxamide (234 mg) as a yellow solid.

Workup

  1. temperatureThe reaction mixture was cooled
  2. washthe organic phase was washed with water and saturated brine
  3. dry with materialAfter drying over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous anunonia=1:0:0-95:4.5:0.5)

Sources & evidence

ORD record
ord-783e8825540443a9865f773491f9c967
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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