Triethylamine → 4-[[4-[4-[3-[2-[2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy]ethoxy]prop-1-ynyl]-2,6-dimethyl-phenoxy]pyrimidin-2-yl]amino]benzonitrile

HRID 1893145Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1893145
I[C:2]1[CH:23]=[C:22]([CH3:24])[C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)[N:8]=2)=[C:4]([CH3:25])[CH:3]=1.[CH2:26]([O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][OH:41])[C:27]#[CH:28].C(N(CC)CC)C>CN(C=O)C.C1COCC1.C(Cl)Cl.CO.[Cu]I.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>[OH:41][CH2:40][CH2:39][O:38][CH2:37][CH2:36][O:35][CH2:34][CH2:33][O:32][CH2:31][CH2:30][O:29][CH2:26][C:27]#[C:28][C:2]1[CH:23]=[C:22]([CH3:24])[C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)[N:8]=2)=[C:4]([CH3:25])[CH:3]=1

Komponenten

9

Edukt 3

HCID 8471TriethylamineHCID 159170603,6,9,12-Tetraoxapentadec-14-yn-1-olHCID 585605744-[4-(4-Iodo-2,6-dimethylphenoxy)pyrimidin-2-ylamino]benzonitrile

Produkt 1

HCID 585605804-[[4-[4-[3-[2-[2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy]ethoxy]prop-1-ynyl]-2,6-dimethyl-phenoxy]pyrimidin-2-yl]amino]benzonitrileAusbeute 85,4 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 21226129Dichloromethane methanolLösungsmittel2×

Versuchsvorschrift

To a deoxygenated solution of iodopyrimidine 3 (494 mg, 1.12 mmol) and 2-(2-(2-(2-(prop-2-ynyloxy)ethoxy)ethoxy)ethoxy)ethanol (Veciani, et al., Ibid.) (780 mg, 3.36 mmol) in dry DMF (1.5 mL) and dry THF (3.0 mL) were added successively dry triethylamine (562.0 mg, 5.55 mmol, 0.80 mL), copper (1) iodide (105.7 mg, 0.56 mmol), and tetrakis(triphenylphosphine)palladium (0) (128.3 mg, 0.11 mmol). The reaction mixture was stirred at 25° C. under a nitrogen atmosphere for 3 hours after which TLC (DCM/methanol=3:97) revealed a more polar product and consumption of starting material 3. The mixture was poured into EDTA solution (20 mL, 5%) and the organic product extracted into EtOAc (3×50 mL). The combined organic extracts were washed with brine (20 mL), dried over Na2SO4 and the solvent evaporated in vacuo to furnish a residue that was subjected to silica-gel column chromatography using DCM/MeOH (95:5) as eluent to produce 4 as a light-brown oil (522.0 mg, 0.956 mmol, 85%).

Aufarbeitung

  1. customa more polar product and consumption of starting material 3
  2. additionThe mixture was poured into EDTA solution (20 mL, 5%)
  3. extractionthe organic product extracted into EtOAc (3×50 mL)
  4. washThe combined organic extracts were washed with brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. customthe solvent evaporated in vacuo
  7. customto furnish a residue that

Quellen und Nachweise

ORD-Eintrag
ord-aae2c27c736c4215939ec13b1d6033ba
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08513205B2

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