Trifluoroacetic acid → HCID 117666901, compound

HRID 1526269Notes

Reaction equation

HRID 1526269 reaction equation
[C:1]([C:4]1[N:5]=[C:6]([CH2:42][CH3:43])[C:7]([NH:30][CH:31]2[CH2:34][N:33]([C:35](OC(C)(C)C)=[O:36])[CH2:32]2)=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][CH:20]([N:23]3[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]3)[CH2:19][CH2:18]2)=[CH:13][CH:12]=1)(=[O:3])[NH2:2].F[C:45](F)(F)[C:46](O)=O>ClCCl>[C:35]([N:33]1[CH2:34][CH:31]([NH:30][C:7]2[N:8]=[C:9]([NH:10][C:11]3[CH:12]=[CH:13][C:14]([N:17]4[CH2:22][CH2:21][CH:20]([N:23]5[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]5)[CH2:19][CH2:18]4)=[CH:15][CH:16]=3)[C:4]([C:1]([NH2:2])=[O:3])=[N:5][C:6]=2[CH2:42][CH3:43])[CH2:32]1)(=[O:36])[CH:45]=[CH2:46]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117666863HCID 117666863, compound

Product 1

HCID 117666901HCID 117666901, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of tert-butyl 3-{[5-carbamoyl-3-ethyl-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]amino}azetidine-1-carboxylate (130 mg), and dichloromethane (1 mL) was added trifluoroacetic acid (1 mL) at 0° C., followed by stirring for 2 hours. The solvent was evaporated, and subjected to liquid separation by the addition of chloroform and a saturated aqueous sodium hydrogen carbonate solution. The organic phase was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. To a mixture of the obtained residue and chloroform (4 mL) were added diisopropylethylamine (140 μL) and acryloyl chloride (40 μL) under ice-cooling, followed by stirring at room temperature for 8 hours. The reactant was subjected to liquid separation by the addition of a saturated aqueous sodium hydrogen carbonate solution. The organic phase was washed with a saturated aqueous sodium hydrogen carbonate solution, and saturated brine 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=1:0:0-100:10:1) to obtain 5-[(1-acryloylazetidin-3-yl)amino]-6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (18 mg).

Workup

  1. customThe solvent was evaporated
  2. customsubjected to liquid separation by the addition of chloroform
  3. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. additionTo a mixture of the obtained residue and chloroform (4 mL)
  7. additionwere added diisopropylethylamine (140 μL) and acryloyl chloride (40 μL) under ice-
  8. temperaturecooling
  9. stirringby stirring at room temperature for 8 hours
  10. customThe reactant was subjected to liquid separation by the addition of a saturated aqueous sodium hydrogen carbonate solution
  11. washThe organic phase was washed with a saturated aqueous sodium hydrogen carbonate solution, and saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customthe solvent was evaporated under reduced pressure
  14. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1)

Sources & evidence

ORD record
ord-c16f1e29854548a0bdffb61c84f6ae1b
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

Loading…