Propargyl alcohol → (4-Cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-{2-[2,5-dichloro-4-(3-hydroxy-prop-1-ynyl)-phenoxy]-pyridin-3-yl}-methanone

HRID 1877420Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1877420
Br[C:2]1[C:29]([Cl:30])=[CH:28][C:5]([O:6][C:7]2[C:12]([C:13]([N:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[N:18]([CH:25]4[CH2:27][CH2:26]4)[CH2:17][CH2:16]3)=[O:14])=[CH:11][CH:10]=[CH:9][N:8]=2)=[C:4]([Cl:31])[CH:3]=1.[CH2:32]([OH:35])[C:33]#[CH:34]>C(N(CC)CC)C.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.[Cu]I>[CH:25]1([N:18]2[C:19]3[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:15]([C:13]([C:12]3[C:7]([O:6][C:5]4[CH:28]=[C:29]([Cl:30])[C:2]([C:34]#[C:33][CH2:32][OH:35])=[CH:3][C:4]=4[Cl:31])=[N:8][CH:9]=[CH:10][CH:11]=3)=[O:14])[CH2:16][CH2:17]2)[CH2:27][CH2:26]1

Komponenten

6

Edukt 2

HCID 7859Propargyl alcoholHCID 59294468[2-(4-Bromo-2,5-dichloro-phenoxy)-pyridin-3-yl]-(4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone

Produkt 1

HCID 59294507(4-Cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-{2-[2,5-dichloro-4-(3-hydroxy-prop-1-ynyl)-phenoxy]-pyridin-3-yl}-methanoneAusbeute 52,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a degassed suspension of [2-(4-bromo-2,5-dichloro-phenoxy)-pyridin-3-yl]-(4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone (100 mg, 0.19 mmol, 1.0 equiv; Example 163) in triethylamine (0.8 mL) under Ar was added 2-propyn-1-ol (216 mg, 220 μL, 3.85 mmol, 20 equiv; [CAS RN 107-19-7]), tetrakis(triphenylphosphine)palladium(0) (22 mg, 0.02 mmol, 0.1 equiv; [CAS RN 14221-01-3]) and copper(I) iodide (3.7 mg, 0.02 mmol, 0.1 equiv; [CAS RN 7681-65-4]). The reaction mixture was heated by microwave irradiation to 100° C. for 1 h. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 49 mg (52%) of the title compound as an off-white powder. MS (ISP): 494.3 [M+H]+.

Aufarbeitung

  1. customRemoval of the solvent mixture
  2. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  3. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  4. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Quellen und Nachweise

ORD-Eintrag
ord-6d855373d7bc45c1a3dff54b0e5ad29e
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08309734B2

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