3-Amino-2-pyrazinecarboxylic acid → HCID 24831021, Verbindung

HRID 446900

Reaktionsgleichung

Reaktionsgleichung von HRID 446900
[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:10]=[CH:11][C:12]3[N:13]([C:15]([C@H:18]([NH:20][C:21](=O)[O:22]C(C)(C)C)[CH3:19])=[N:16][N:17]=3)[N:14]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:28][C:29]1[C:30](C(O)=O)=[N:31][CH:32]=[CH:33][N:34]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:10]=[CH:11][C:12]3[N:13]([C:15]([C@H:18]([NH:20][C:21]([C:30]4[C:29]([NH2:28])=[N:34][CH:33]=[CH:32][N:31]=4)=[O:22])[CH3:19])=[N:16][N:17]=3)[N:14]=2)[CH:5]=[CH:6][CH:7]=1

Komponenten

7

Edukt 4

HCID 726563-Amino-2-pyrazinecarboxylic acidHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59363286HCID 59363286, Verbindung

Produkt 1

HCID 24831021HCID 24831021, VerbindungAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 21863450Trifluoroacetic acid methylene chlorideLösungsmittel

Versuchsvorschrift

(Steps 1-v & 1-yl) tert-Butyl (R)-1-(6-(3-chlorophenylamino)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethylcarbamate (110 mg, 0.28 mmol) was dissolved in 5 mL TFA/CH2Cl2 (1:1) and left standing for 20 min. The solvent was removed under reduced pressure and CH2Cl2 was added and removed 4 times to remove residual TFA. The resulting amine was dissolved in DMF and 3-aminopyrazine-2-carboxylic acid (200 mg, 1.4 mmol), HBTU (0.50 g, 1.3 mmol) and DIEA (1 mL, 5.7 mmol) were added. The reaction mixture was stirred at room temperature for 2 hours, then poured into ethyl acetate/0.1 M NaOH. The organic layer was dried over sodium sulfate and concentrated to yield an oil. This oil was purified by reversed-phase HPLC. Fractions containing pure product were concentrated to give N—((R)-1-(6-(3-chlorophenylamino)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)-3-aminopyrazine-2-carboxamide as a yellow solid (60 mg, 0.13 mmol, 48% yield): 1H NMR (500 MHz, DMSO-d6) 10.43 (s, 1H), 9.19 (d, J=8.1 Hz, 1H), 8.22-8.20 (m, 2H), 7.89 (t, J=2.0 Hz, 1H), 7.75-7.73 (m, 2H), 7.33 (m, 2H), 7.07 (dd, J=1.3, 7.9 Hz, 1H), 5.76-5.71 (m, 1H), 1.75 (d, J=6.9 Hz, 3H); MH+410.2.

Aufarbeitung

  1. waitleft
  2. customThe solvent was removed under reduced pressure and CH2Cl2
  3. additionwas added
  4. customremoved 4 times
  5. customto remove residual TFA
  6. dissolutionThe resulting amine was dissolved in DMF
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated
  9. customto yield an oil
  10. customThis oil was purified by reversed-phase HPLC
  11. additionFractions containing pure product
  12. concentrationwere concentrated

Quellen und Nachweise

ORD-Eintrag
ord-0c1043e14e824b4a8732a27346497ae6
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481538B2

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