Picolinic acid → HCID 57513840, Verbindung

HRID 2368435Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2368435
[NH2:1][C:2]([CH3:26])([CH3:25])[C:3]([NH:5][C:6]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[N:8]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:7]=1)=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N:51]1[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=1[C:57](O)=[O:58]>C(Cl)Cl.CCOC(C)=O>[CH2:18]([N:8]1[C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[N:10][C:6]([NH:5][C:3]([C:2]([NH:1][C:57]([C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][N:51]=2)=[O:58])([CH3:26])[CH3:25])=[O:4])=[N:7]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Komponenten

6

Edukt 3

HCID 1018Picolinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57513839HCID 57513839, Verbindung

Produkt 1

HCID 57513840HCID 57513840, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

2-Amino-N-[1-benzyl-5-(4-fluoro-phenyl)-1H-[1,2,4]triazol-3-yl]-2-methyl-propionamide (137 mg, 0.388 mmol), HATU (295 mg, 0.776 mmol), and picolinic acid (72 mg, 0.582 mmol) were stirred in DCM (6 mL). TEA (108 uL, 0.776 mmol) was added to the reaction mixture and it was stirred for 1 day. It was diluted with EtOAc (65 mL) and extracted with water (15 mL), followed by saturated NaHCO3 (15 mL). The organic layer was dried with a brine wash (10 mL) followed by Na2SO4. The solvents were removed in vacuo and the residue was purified by reverse phase HPLC (C18, 45-100% MeOH/H2O+5 mM NH4OH) followed by silica gel chromatography (0-30% ACN/DCM) to afford the title compound as a white solid: 1H NMR (400 MHz, DICHLOROMETHANE-d2) δ ppm 1.73 (s, 6H) 5.35 (s, 2H) 7.07-7.22 (m, 4H) 7.26-7.39 (m, 3H) 7.49 (ddd, J=7.61, 4.77, 1.14 Hz, 1H) 7.52-7.61 (m, 2H) 7.90 (td, J=7.74, 1.71 Hz, 1H) 8.19 (dt, J=7.77, 1.04 Hz, 1H) 8.47 (br. s., 1H) 8.58 (ddd, J=4.77, 1.61, 0.95 Hz, 1H) 9.45 (br. s., 1H); Rt (method A)=1.22 min, (M+H)+ 459.0.

Aufarbeitung

  1. extractionextracted with water (15 mL)
  2. dry with materialThe organic layer was dried with a brine
  3. washwash (10 mL)
  4. customThe solvents were removed in vacuo
  5. customthe residue was purified by reverse phase HPLC (C18, 45-100% MeOH/H2O+5 mM NH4OH)

Quellen und Nachweise

ORD-Eintrag
ord-d6167d5f95024ffca43a989e78ad9521
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08703761B2

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