Dimethylformamide → 6-isopropyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(3-{[(2E)-4-(morpholin-4-yl)but-2-enoyl]amino}phenoxy)pyrazine-2-carboxamide

HRID 1526264Notes

Reaction equation

HRID 1526264 reaction equation
Cl[CH2:2]/[CH:3]=[CH:4]/[C:5]([NH:7][C:8]1[CH:9]=[C:10]([CH:38]=[CH:39][CH:40]=1)[O:11][C:12]1[N:13]=[C:14]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([N:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)=[CH:27][CH:26]=2)[C:15]([C:21]([NH2:23])=[O:22])=[N:16][C:17]=1[CH:18]([CH3:20])[CH3:19])=[O:6].CN(C)C=O.C(N(C(C)C)CC)(C)C.[NH:55]1[CH2:60][CH2:59][O:58][CH2:57][CH2:56]1>O>[CH:18]([C:17]1[N:16]=[C:15]([C:21]([NH2:23])=[O:22])[C:14]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([N:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)=[CH:27][CH:26]=2)=[N:13][C:12]=1[O:11][C:10]1[CH:38]=[CH:39][CH:40]=[C:8]([NH:7][C:5](=[O:6])/[CH:4]=[CH:3]/[CH2:2][N:55]2[CH2:60][CH2:59][O:58][CH2:57][CH2:56]2)[CH:9]=1)([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 1176675045-(3-{[(2E)-4-chlorobuta-2-enoyl]amino}phenoxy)-6-isopropyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide

Product 1

HCID 1176670646-isopropyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(3-{[(2E)-4-(morpholin-4-yl)but-2-enoyl]amino}phenoxy)pyrazine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 5-(3-{[(2E)-4-chlorobuta-2-enoyl]amino}phenoxy)-6-isopropyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (80 mg) and N,N-dimethylformamide (800 μL) were added diisopropylethylamine (25 μL) and morpholine (11 μL), followed by stirring at room temperature overnight. Water was added thereto, and the precipitated solid was collected by filtration and purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1). Diisopropyl ether was added thereto and the precipitated solid was collected by filtration and then dried under reduced pressure to obtain 6-isopropyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(3-{[(2E)-4-(morpholin-4-yl)but-2-enoyl]amino}phenoxy)pyrazine-2-carboxamide (27 mg) as a solid.

Workup

  1. filtrationthe precipitated solid was collected by filtration
  2. custompurified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1)
  3. additionDiisopropyl ether was added
  4. filtrationthe precipitated solid was collected by filtration
  5. customdried under reduced pressure

Sources & evidence

ORD record
ord-7edf2575c93d49baa3bb381e838c2622
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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