Hydroxide → 3-amino-N-methyl-6-[3-({[(3-morpholin-4-ylphenyl)methyl]amino}methyl) phenyl]pyrazine-2-carboxamide

HRID 646677Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 646677
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:12]2[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=2)[C:15](O)=O)=[N:6][C:7]=1[C:8]([NH:10][CH3:11])=[O:9].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O.[N:62]1([C:68]2[CH:69]=[C:70]([CH2:74][NH2:75])[CH:71]=[CH:72][CH:73]=2)[CH2:67][CH2:66][O:65][CH2:64][CH2:63]1.[OH-]>CN(C=O)C>[NH2:1][C:2]1[C:7]([C:8]([NH:10][CH3:11])=[O:9])=[N:6][C:5]([C:12]2[CH:20]=[CH:19][CH:18]=[C:14]([CH2:15][NH:75][CH2:74][C:70]3[CH:71]=[CH:72][CH:73]=[C:68]([N:62]4[CH2:67][CH2:66][O:65][CH2:64][CH2:63]4)[CH:69]=3)[CH:13]=2)=[CH:4][N:3]=1

Komponenten

7

Edukt 5

HCID 961HydroxideHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 587105713-{5-Amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acidHCID 68650468[(3-Morpholin-4-ylphenyl)methyl]amine trifluoroacetate

Produkt 1

HCID 686518413-amino-N-methyl-6-[3-({[(3-morpholin-4-ylphenyl)methyl]amino}methyl) phenyl]pyrazine-2-carboxamideAusbeute 10,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

A solution of 3-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoic acid (0.081 g, 0.30 mmol), HOBt (0.048 g, 0.36 mmol) and HBTU (0.17 g, 0.45 mmol) in DMF (1.0 mL) was stirred at r.t. for 10 min. A solution of [(3-morpholin-4-ylphenyl)methyl]amine trifluoroacetate (0.13 g, 0.30 mmol) in DMF (1.0 mL) was added and the resulting solution was stirred for 12 h at r.t. The solution was concentrated in vacuo and the crude mixture was purified via HPLC (reverse-phase, CH3CN/H2O with 0.1% TFA). Upon removal of CH3CN/H2O, the product was taken up in EtOAc (100 mL) and washed with 1M NaOH(aq) (50 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. Trituration and collection of a solid by vacuum filtration provided 11.6 mg (and treated with Bio-Rad AG 1-X8 resin (hydroxide form) until pH 8. The product was filtered and concentrated in vacuo, to provide 14.1 mg (9% yield) of 3-amino-N-methyl-6-[3-({[(3-morpholin-4-ylphenyl)methyl]amino}methyl) phenyl]pyrazine-2-carboxamide: 1H NMR (400 MHz, d6-DMSO): 9.15 (t, 1H), 8.91 (s, 1H), 8.87 (m, 1H), 8.55 (s, 1H), 8.37 (d, 1H), 7.88 (d, 1H), 7.57 (t, 1H), 7.19 (t, 1H), 6.95 (s, 1H), 6.82 (m, 2H), 4.48 (d, 2H), 3.72 (t, 4H), 3.08 (t, 2H), 2.85 (d, 3H); MS (EI) for C24H26N6O3: 447 (MH+).

Aufarbeitung

  1. concentrationThe solution was concentrated in vacuo
  2. customthe crude mixture was purified via HPLC (reverse-phase, CH3CN/H2O with 0.1% TFA)
  3. customUpon removal of CH3CN/H2O
  4. washwashed with 1M NaOH(aq) (50 mL)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customTrituration and collection of a solid
  9. filtrationby vacuum filtration
  10. customprovided 11.6 mg (and
  11. additiontreated with Bio-Rad AG
  12. filtrationThe product was filtered
  13. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-2c75d91355494f3fa77cec80736ed7d8
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07704995B2

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