Dimethylformamide → Tert-butyl 3-[(5-carbamoyl-3-ethyl-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazin-2-yl)oxy]pyrrolidine-1-carboxylate

HRID 1526189Notes

Reaction equation

HRID 1526189 reaction equation
[C:1]([C:4]1[N:5]=[C:6]([CH2:24][CH3:25])[C:7]([O:11][CH:12]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]2)=[N:8][C:9]=1Cl)(=[O:3])[NH2:2].[CH3:26][N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:39]=[CH:38][C:36]([NH2:37])=[CH:35][CH:34]=2)[CH2:29][CH2:28]1.C(N(C(C)C)CC)(C)C.CN(C)C=O>C(OCC)(=O)C>[C:1]([C:4]1[N:5]=[C:6]([CH2:24][CH3:25])[C:7]([O:11][CH:12]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]2)=[N:8][C:9]=1[NH:37][C:36]1[CH:35]=[CH:34][C:33]([N:30]2[CH2:29][CH2:28][N:27]([CH3:26])[CH2:32][CH2:31]2)=[CH:39][CH:38]=1)(=[O:3])[NH2:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 7372534-(4-Methylpiperazin-1-yl)anilineHCID 117666931Tert-butyl 3-[(5-carbamoyl-6-chloro-3-ethylpyrazin-2-yl)oxy]pyrrolidine-1-carboxylate

Product 1

HCID 117667557Tert-butyl 3-[(5-carbamoyl-3-ethyl-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazin-2-yl)oxy]pyrrolidine-1-carboxylateYield 31.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of tert-butyl 3-[(5-carbamoyl-6-chloro-3-ethylpyrazin-2-yl)oxy]pyrrolidine-1-carboxylate (790 mg), 4-(4-methylpiperazin-1-yl)aniline (448 mg), diisopropylethylamine (729 μL), and N,N-dimethylformamide (5.53 mL) was stirred at 120° C. for 22 hours. The reaction mixture was left to be cooled and then diluted with ethyl acetate, and the organic phase was washed with water, a saturated aqueous sodium hydrogen carbonate solution, and saturated brine in this order, and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-30:1:0.1), and then washed with diisopropyl ether to obtain tert-butyl 3-[(5-carbamoyl-3-ethyl-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazin-2-yl)oxy]pyrrolidine-1-carboxylate (355 mg) as a pale yellow solid.

Workup

  1. waitThe reaction mixture was left
  2. temperatureto be cooled
  3. washthe organic phase was washed with water
  4. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and saturated brine in this order, and dried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-30:1:0.1)
  7. washwashed with diisopropyl ether

Sources & evidence

ORD record
ord-3d7031c38c0646f69ffb364fbf2ed297
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

Loading…