Cesium carbonate → (2-Chloro-4-(3-(quinolin-6-ylmethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)methanol

HRID 40282

Reaktionsgleichung

Reaktionsgleichung von HRID 40282
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]=[CH:17][CH:16]=[CH:15]4)=[N:9][N:10]=2)[N:7]=1.[Cl:22][C:23]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[CH:25][C:24]=1[CH2:38][OH:39].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[Cl:22][C:23]1[CH:28]=[C:27]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([CH2:11][C:12]4[CH:13]=[C:14]5[C:19](=[CH:20][CH:21]=4)[N:18]=[CH:17][CH:16]=[CH:15]5)=[N:9][N:10]=3)[N:7]=2)[CH:26]=[CH:25][C:24]=1[CH2:38][OH:39]

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 249683676-((6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)quinolineHCID 57691187(2-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol

Produkt 1

HCID 57691098(2-Chloro-4-(3-(quinolin-6-ylmethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)methanol

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 53485975CID 53485975KatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A suspension of 6-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)quinoline (170 mg, 575 μmol), (2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol (309 mg, 1150 μmol), dichloro[1,1′bis(diphenylphoshino)ferrocene]palladium(ii)dichloromethane adduct (126 mg, 172 μmol), cesium carbonate (749 mg, 2299 μmol) in Dioxane (0.3 mL) and water (0.3 mL) was sparged with argon for 5 min then heated to 100° C. with stirring. 1:30 am. After 90 min, LCMS suggests 95% conversion. Reaction then partitioned between 9:1 CHCl3/IPA (25 mL) and 5% NaHCO3 (15 mL). Aqueous further extracted with 9:1 CHCl3/IPA (2×10 mL). Combined organics dried with MgSO4, concentrated onto dry silica (10 g), and then purified on silica (12 g) eluting with 0>10% 2M NH3 in MeOH/DCM. Resulting solid triturated with methanol (2 mL) and collected by filtration. MS (ESI pos. ion) m/z: 402 (MH+). Calc'd exact mass for C22H16ClN5O: 401.

Aufarbeitung

  1. customwas sparged with argon for 5 min
  2. customReaction
  3. customthen partitioned between 9:1 CHCl3/IPA (25 mL) and 5% NaHCO3 (15 mL)
  4. extractionAqueous further extracted with 9:1 CHCl3/IPA (2×10 mL)
  5. dry with materialCombined organics dried with MgSO4
  6. concentrationconcentrated onto dry silica (10 g)
  7. custompurified on silica (12 g)
  8. washeluting with 0>10% 2M NH3 in MeOH/DCM
  9. customResulting solid
  10. customtriturated with methanol (2 mL)
  11. filtrationcollected by filtration

Quellen und Nachweise

ORD-Eintrag
ord-7672878a3bdd42b3b523b8ed14de38bc
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524900B2

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