Acetic Anhydride → 1-(4-(5,7-Difluoro-3-methyl-4-(5-morpholinopyridin-3-ylamino)quinolin-2-yl)piperazin-1-yl)ethanone

HRID 1431658Notes

Reaction equation

HRID 1431658 reaction equation
FC1C=C(F)C=C2C=1C(NC1C=NC=C(N3CCOCC3)C=1)=C(C)C(N1CCNCC1)=N2.C(N(CC)CC)C.C(OC(=O)C)(=O)C.[F:47][C:48]1[CH:57]=[C:56]([F:58])[CH:55]=[C:54]2[C:49]=1[C:50]([NH:69][C:70]1[CH:71]=[N:72][CH:73]=[C:74]([N:76]3[CH2:81][CH2:80][O:79][CH2:78][CH2:77]3)[CH:75]=1)=[C:51]([CH3:68])[C:52]([N:59]1[CH2:64][CH2:63][N:62]([C:65](=[O:67])[CH3:66])[CH2:61][CH2:60]1)=[N:53]2.C(=O)(O)[O-].[Na+]>C1COCC1>[F:47][C:48]1[CH:57]=[C:56]([F:58])[CH:55]=[C:54]2[C:49]=1[C:50]([NH:69][C:70]1[CH:71]=[N:72][CH:73]=[C:74]([N:76]3[CH2:77][CH2:78][O:79][CH2:80][CH2:81]3)[CH:75]=1)=[C:51]([CH3:68])[C:52]([N:59]1[CH2:64][CH2:63][N:62]([C:65](=[O:67])[CH3:66])[CH2:61][CH2:60]1)=[N:53]2

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 596310285,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(piperazin-1-yl)quinolin-4-amineHCID 68785587Sodium bicarbonate 1-(4-(5,7-difluoro-3-methyl-4-(5-morpholinopyridin-3-ylamino)quinolin-2-yl)piperazin-1-yl)ethanone

Product 1

HCID 596315151-(4-(5,7-Difluoro-3-methyl-4-(5-morpholinopyridin-3-ylamino)quinolin-2-yl)piperazin-1-yl)ethanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The 5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(piperazin-1-yl)-quinolin-4-amine (50 mg, 0.11 mmol) was dissolved in THF (1.1 mL) and the triethylamine (24.0 μL, 0.17 mmol) and acetic anhydride (11.0 μL, 0.11 mmol) were added and the mixture was stirred overnight. The reaction was then quenched with water and extracted with EtOAc. The organic layers were dried over magnesium sulfate and the filtrate was cond. The crude material was purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 95% over 20 min to provide, after treatment with sodium bicarbonate 1-(4-(5,7-difluoro-3-methyl-4-(5-morpholinopyridin-3-ylamino)quinolin-2-yl)piperazin-1-yl)ethanone: 1H NMR (CDCl3) δ ppm 8.22 (1H, d, J=7.6 Hz), 7.88 (1H, d, J=2.2 Hz), 7.82 (1H, d, J=1.8 Hz), 7.49 (1H, dd, J=9.6, 1.2 Hz), 7.14-7.23 (1H, m), 6.86 (1H, ddd, J=13.0, 8.4, 2.3 Hz), 3.77-3.95 (6H, m), 3.61-3.76 (4H, m), 3.53-3.61 (2H, m), 3.23-3.37 (4H, m), 2.19 (3H, s), 2.16 (3H, s). Mass Spectrum (ESI) m/e=483.3 (M+1).

Workup

  1. customThe reaction was then quenched with water
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layers were dried over magnesium sulfate
  4. customThe crude material was purified by reverse-phase preparative HPLC
  5. customover 20 min
  6. customto provide

Sources & evidence

ORD record
ord-a896adb59ca04187ac44bc823660dc50
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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