Trichloroacetonitrile → 6-(Difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)quinoline

HRID 219254

Reaktionsgleichung

Reaktionsgleichung von HRID 219254
[F:1][C:2]1[C:3]([NH:14][NH2:15])=[N:4][CH:5]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=2)[CH:7]=1.[F:16][C:17]([F:32])([C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[N:28]=[CH:27][CH:26]=[CH:25]2)[C:18](OC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCN(C(C)C)C(C)C.ClC(Cl)(Cl)C#N>C(Cl)Cl>[F:32][C:17]([F:16])([C:18]1[N:4]2[CH:5]=[C:6]([C:8]3[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=3)[CH:7]=[C:2]([F:1])[C:3]2=[N:14][N:15]=1)[C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[N:28]=[CH:27][CH:26]=[CH:25]2

Komponenten

7

Edukt 5

HCID 11011TrichloroacetonitrileHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 58955252Methyl 2,2-difluoro-2-(quinolin-6-yl)acetateHCID 675032383-fluoro-2-hydrazinyl-5-(1-methyl-1H-pyrazol-4-yl)pyridine

Produkt 1

HCID 441814606-(Difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)quinoline

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a stirring suspension of 1-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)hydrazine (190 mg, 917 μmol), methyl 2,2-difluoro-2-(quinolin-6-yl)acetate (218 mg, 917 μmol), triphenylphosphine polymer supported (241 mg, 917 μmol), DIEA (200 μl, 1146 μmol) in DCM (4 mL) was added 2,2,2-trichloroacetonitrile (92 μl, 917 μmol). The reaction vessel was then appropriately sealed and heated to 150° C. with microwaves for 15 min. The reaction was then concentrated onto dry silica under reduced pressure and product purified on silica (40 g) eluting with 1-4% of 2 M NH3 in MeOH/DCM. The product was then further purified by RP-HPLC eluting with water/ACN (0.1% TFA). Collected fractions concentrated under reduced pressure, dissolved in MeOH/DCM (5 mL) and stirred with Si-Carbonated (300 mg; 0.2 mmol) for 30 min at 23° C. Solids were then removed by filtration, and washed with MeOH (3×1 mL). The filtrate was then concentrated under reduced pressure, and product isolated as an off white solid. MS (ESI pos. ion) m/z: 395 (MH+). Calc'd exact mass for C20H13F3N6: 394.

Aufarbeitung

  1. customThe reaction vessel was then appropriately sealed
  2. concentrationThe reaction was then concentrated onto dry silica under reduced pressure and product
  3. custompurified on silica (40 g)
  4. washeluting with 1-4% of 2 M NH3 in MeOH/DCM
  5. customThe product was then further purified by RP-HPLC
  6. washeluting with water/ACN (0.1% TFA)
  7. customCollected
  8. concentrationfractions concentrated under reduced pressure
  9. dissolutiondissolved in MeOH/DCM (5 mL)
  10. customSolids were then removed by filtration
  11. washwashed with MeOH (3×1 mL)
  12. concentrationThe filtrate was then concentrated under reduced pressure, and product
  13. customisolated as an off white solid

Quellen und Nachweise

ORD-Eintrag
ord-181280c49e8c44118e145ea455427ae1
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08198448B2

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