Tetrahydrofuran → 5-(3-Aminophenoxy)-6-(2-hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide

HRID 1526172Notes

Reaction equation

HRID 1526172 reaction equation
[OH:1][C:2]([C:5]1[N:10]=[C:9]([C:11]([NH2:13])=[O:12])[C:8]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)=[N:7][C:6]=1[O:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([N+:35]([O-])=O)[CH:30]=1)([CH3:4])[CH3:3].O1CCCC1.S(S([O-])=O)([O-])=O.[Na+].[Na+].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(O)(C)C.O.CO>[NH2:35][C:31]1[CH:30]=[C:29]([CH:34]=[CH:33][CH:32]=1)[O:28][C:6]1[N:7]=[C:8]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([N:21]3[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]3)=[CH:19][CH:20]=2)[C:9]([C:11]([NH2:13])=[O:12])=[N:10][C:5]=1[C:2]([OH:1])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 24489Sodium DithioniteHCID 516892Sodium BicarbonateHCID 1176669966-(2-Hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(3-nitrophenoxy)pyrazine-2-carboxamide

Product 1

HCID 1176673885-(3-Aminophenoxy)-6-(2-hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamideYield 9.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Procedure

To a mixture of 6-(2-hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(3-nitrophenoxy)pyrazine-2-carboxamide (300 mg), tetrahydrofuran (6 mL), and methanol (12 mL) were added sodium dithionite (1.03 g), sodium hydrogen carbonate (993 mg), and water (13.5 mL), followed by stirring at room temperature for 30 minutes, and then stirring at 50° C. for 2 hours. To the reaction mixture was added chloroform-isopropanol (4:1), and then the organic phase was washed with water. The organic phase was dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH2 type, eluent; chloroform:methanol:28% aqueous ammonia=50:1:0.1-20:1:0.1) to obtain 5-(3-aminophenoxy)-6-(2-hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (27 mg) as a yellow solid.

Workup

  1. stirringstirring at 50° C. for 2 hours
  2. washthe organic phase was washed with water
  3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (NH2 type, eluent; chloroform:methanol:28% aqueous ammonia=50:1:0.1-20:1:0.1)

Sources & evidence

ORD record
ord-b2a86d59db644d22a0aa427375c68fad
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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