N-methyl-2-pyrrolidone → 3-{[1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl]amino}-5-(3-nitrophenoxy)-6-(prop-1-en-2-yl)pyrazine-2-carboxamide

HRID 1526175Notes

Reaction equation

HRID 1526175 reaction equation
Cl[C:2]1[C:3]([C:22]([NH2:24])=[O:23])=[N:4][C:5]([C:18](O)([CH3:20])[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.[CH3:25][N:26]1[CH2:31][CH2:30][CH:29]([N:32]2[CH:36]=[C:35]([NH2:37])[CH:34]=[N:33]2)[CH2:28][CH2:27]1.C(N(C(C)C)CC)(C)C.CN1CCCC1=O>[Cl-].[Na+].O.O>[CH3:25][N:26]1[CH2:27][CH2:28][CH:29]([N:32]2[CH:36]=[C:35]([NH:37][C:2]3[C:3]([C:22]([NH2:24])=[O:23])=[N:4][C:5]([C:18]([CH3:20])=[CH2:19])=[C:6]([O:8][C:9]4[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=4)[N:7]=3)[CH:34]=[N:33]2)[CH2:30][CH2:31]1

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 533023461-(1-methylpiperidin-4-yl)-1H-pyrazol-4-amineHCID 1176669023-Chloro-6-(2-hydroxypropan-2-yl)-5-(3-nitrophenoxy)pyrazine-2-carboxamide

Product 1

HCID 1176670793-{[1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl]amino}-5-(3-nitrophenoxy)-6-(prop-1-en-2-yl)pyrazine-2-carboxamideYield 52.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 3-chloro-6-(2-hydroxypropan-2-yl)-5-(3-nitrophenoxy)pyrazine-2-carboxamide (300 mg), 1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-amine (184 mg), diisopropylethylamine (291 μL), and N-methylpyrrolidone (3 mL) was reacted in a microwave reaction device at 180° C. for 2 hours. To the reaction mixture were added water and saturated brine, followed by extraction with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1). The obtained solid was purified by silica gel column chromatography (NH2 type, eluent; chloroform:methanol=100:0-98:2) to obtain 3-{[1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl]amino}-5-(3-nitrophenoxy)-6-(prop-1-en-2-yl)pyrazine-2-carboxamide (212 mg) as a yellow solid.

Workup

  1. customwas reacted in a microwave reaction device at 180° C. for 2 hours
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1)
  6. customThe obtained solid was purified by silica gel column chromatography (NH2 type, eluent; chloroform:methanol=100:0-98:2)

Sources & evidence

ORD record
ord-1c66a7fc4fa7463c9a78e8797b57f5c9
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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