3-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine → 5-(5-bromo-2-(piperazin-1-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine

HRID 1091621

Reaktionsgleichung

Reaktionsgleichung von HRID 1091621
[CH3:1][O:2][C:3]1[C:4]([NH2:18])=[N:5][CH:6]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:8]=1.Br[C:20]1[N:21]=[C:22]([N:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)[N:23]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:24]=1[Br:25]>COCCOC.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:25][C:24]1[N:23]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:22]([N:34]2[CH2:35][CH2:36][NH:37][CH2:38][CH2:39]2)=[N:21][C:20]=1[C:7]1[CH:8]=[C:3]([O:2][CH3:1])[C:4]([NH2:18])=[N:5][CH:6]=1

Komponenten

6

Edukt 2

HCID 533980593-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 586258311-(4,5-Dibromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)piperazine

Produkt 1

HCID 665911525-(5-bromo-2-(piperazin-1-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittelHCID 10340Sodium CarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
115 °C

Versuchsvorschrift

A mixture of 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (56.2 mg, 0.225 mmol) and 1-(4,5-dibromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)piperazine (90 mg, 0.204 mmol) in DME (2.1 ml) and 2M aqueous Na2CO3 (0.7 ml) was sparged with Ar for 2 min. Pd(Ph3P)4 (23.6 mg, 0.02 mmol) was added. The mixture was sparged with Argon for an additional 2 min and was heated in a sealed tube in a microwave reactor at 115° C. for 15 min. The reaction mixture was extracted with EtOAc (3×15 mL). The combined organic layers were washed with brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude materials of both reactions were combined and purified by preparative TLC (SiO2, 1.0 mm, 90:10 DCM-MeOH) to furnish 5-(5-bromo-2-(piperazin-1-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine was isolated as a white solid which was directly used in the next step: LCMS (m/z): 485.2 (MH+), tR=0.56 min.

Aufarbeitung

  1. customwas sparged with Ar for 2 min
  2. customThe mixture was sparged with Argon for an additional 2 min
  3. extractionThe reaction mixture was extracted with EtOAc (3×15 mL)
  4. washThe combined organic layers were washed with brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified by preparative TLC (SiO2, 1.0 mm, 90:10 DCM-MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-6e7e0a0437fe4a4baacf578fee589786
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08129394B2

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