Benzaldehyde → HCID 117667673, compound

HRID 1526272Notes

Reaction equation

HRID 1526272 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:25][CH2:24][CH:23]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[CH2:22][CH2:21]3)=[CH:16][CH:15]=2)[C:5]([C:10]([NH2:12])=[O:11])=[N:6][C:7]=1[CH2:8][CH3:9].[NH2:33][CH2:34][CH2:35][N:36]([CH3:44])[C:37](=[O:43])OC(C)(C)C.[CH:45](N(C(C)C)CC)(C)[CH3:46].C(=O)C1C=CC=CC=1>CN(C)C=O.CN1CCCC1=O>[C:37]([N:36]([CH3:44])[CH2:35][CH2:34][NH:33][C:2]1[N:3]=[C:4]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:21][CH2:22][CH:23]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[CH2:24][CH2:25]3)=[CH:16][CH:15]=2)[C:5]([C:10]([NH2:12])=[O:11])=[N:6][C:7]=1[CH2:8][CH3:9])(=[O:43])[CH:45]=[CH2:46]

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 81531DiisopropylethylamineHCID 2756424N-Boc-N-methylethylenediamineHCID 885697085-Chloro-6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide

Product 1

HCID 117667673HCID 117667673, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 5-chloro-6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (21 mg), tert-butyl (2-aminoethyl)methylcarbamate (31 mg), diisopropylethylamine (16 μL), and N-methylpyrrolidone (0.3 mL) was stirred at 140° C. for 2 hours and a half. To the reaction mixture was added PS-benzaldehyde (Biotage, 150 mg) at room temperature, N,N-dimethylformamide (1 mL) was added thereto, followed by stirring for 2 hours, and the insoluble matter was filtered. The filtrate was evaporated under reduced pressure and the obtained residue were added methanol (0.5 mL) and a 4 M hydrogen chloride-dioxane solution (0.45 mL), followed by stirring at room temperature for 8 hours. The solvent was evaporated under reduced pressure, and to the obtained residue were added tetrahydrofuran (0.9 mL) and a saturated aqueous sodium hydrogen carbonate solution (1 mL), followed by stirring at room temperature. Acryloyl chloride (8 μL) and tetrahydrofuran (0.1 mL) were added thereto at room temperature, followed by stirring for 4 hours. The reaction mixture was extracted with chloroform. The solvent of the organic phase was evaporated under reduced pressure and the obtained residue was purified by preparative HPLC (methanol/0.1% aqueous formic acid solution) to obtain 5-({2-[acryloyl (methyl)amino]ethyl}amino)-6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (1 mg).

Workup

  1. stirringby stirring for 2 hours
  2. filtrationthe insoluble matter was filtered
  3. customThe filtrate was evaporated under reduced pressure
  4. additionthe obtained residue were added methanol (0.5 mL)
  5. stirringby stirring at room temperature for 8 hours
  6. customThe solvent was evaporated under reduced pressure
  7. additionto the obtained residue were added tetrahydrofuran (0.9 mL)
  8. stirringby stirring at room temperature
  9. additionAcryloyl chloride (8 μL) and tetrahydrofuran (0.1 mL) were added
  10. customat room temperature
  11. stirringby stirring for 4 hours
  12. extractionThe reaction mixture was extracted with chloroform
  13. customThe solvent of the organic phase was evaporated under reduced pressure
  14. customthe obtained residue was purified by preparative HPLC (methanol/0.1% aqueous formic acid solution)

Sources & evidence

ORD record
ord-b4cdfe82c8e844b9a7be76e2da577c50
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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