Allyl bromide → (R)-N-(1-(5-allyl-1-(5-fluoropyrimidin-2-yl)-1H-1,2,3-triazol-4-yl)ethyl)-2-chloro-3-(trifluoromethyl)benzamide

HRID 2177653

Reaktionsgleichung

Reaktionsgleichung von HRID 2177653
[CH3:1][C@@H:2]([NH:5][C:6](=[O:19])[C:7]1[CH:12]=[C:11](F)[CH:10]=[C:9]([C:14]([F:17])([F:16])[F:15])[C:8]=1[Cl:18])[C:3]#[CH:4].[N:20]1[N:24]2[CH:25]=[CH:26][CH:27]=[N:28][C:23]2=[N:22][N:21]=1.ClC1C=C([F:39])C=CC=1C(Cl)=O.[CH2:40](Br)[CH:41]=[CH2:42].C([O-])([O-])=O.[Cs+].[Cs+]>[Cu]I>[CH2:40]([C:4]1[N:22]([C:23]2[N:28]=[CH:27][C:26]([F:39])=[CH:25][N:24]=2)[N:21]=[N:20][C:3]=1[C@H:2]([NH:5][C:6](=[O:19])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:14]([F:17])([F:16])[F:15])[C:8]=1[Cl:18])[CH3:1])[CH:41]=[CH2:42]

Komponenten

7

Edukt 5

HCID 7841Allyl bromideHCID 10796Cesium carbonateHCID 349391Tetrazolo(1,5-a)pyrimidineHCID 27365462-Chloro-4-fluorobenzoyl chlorideHCID 90409344(R)-N-(but-3-yn-2-yl)-2-chloro-5-fluoro-3-(trifluoromethyl)benzamide

Produkt 1

HCID 90409968(R)-N-(1-(5-allyl-1-(5-fluoropyrimidin-2-yl)-1H-1,2,3-triazol-4-yl)ethyl)-2-chloro-3-(trifluoromethyl)benzamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Katalysator

Versuchsvorschrift

To the suspension of Intermediate 241 (41.93 g, 152.11 mmol, 1.0 equiv), tetrazolo[1,5-a]pyrimidine (Intermediate 234, 25.43 g, 182.85 mmol, 1.2 equiv.), allyl bromide (16.73 mL, 197.74 mmol, 1.3 equiv.) and Cs2CO3(148.68 g, 456.33 mmol, 3.0 equiv.) in 2-methylTHF (1000 mL) was added CuI (28.97 g, 152.11 mmol, 1.0 equiv.) at room temperature in one portion under N2. The reaction mixture was stirred at room temperature under N2(g) for 16 hours. The insoluble solid was filtered off and the filtrate was washed with KOH (700 mL) and EtOAc (300 mL). The organic layer was extracted, dried over Na2SO4 and concentrated. The crude was slurried in 4/1 EtOAc/TMBE 400 mL/100 mL for 48 hours then filtered to recover Intermediate 242: (R)—N-(1-(5-allyl-1-(5-fluoropyrimidin-2-yl)-1H-1,2,3-triazol-4-yl)ethyl)-2-chloro-3-(trifluoromethyl)benzamide as a light yellow solid. (56.5 g, 124.27 mmol, 82%). MS-ESI (m/z): [M+H]+ calcd for C19H15ClF4N6O, 454.81. found, 455.10.

Aufarbeitung

  1. filtrationThe insoluble solid was filtered off
  2. washthe filtrate was washed with KOH (700 mL) and EtOAc (300 mL)
  3. extractionThe organic layer was extracted
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. waitThe crude was slurried in 4/1 EtOAc/TMBE 400 mL/100 mL for 48 hours
  7. filtrationthen filtered
  8. customto recover Intermediate 242

Quellen und Nachweise

ORD-Eintrag
ord-80a5eb542e6846ad8fb541a1df262c23
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09066946B2

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