Triethylamine → 2-Methylsulfanyl-5-(2-methylphenyl)ethynylpyrimidine-4-carboxylic acid methyl ester

HRID 556337Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 556337
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH3:9])#[CH:2].[CH3:10][O:11][C:12]([C:14]1[C:19](Br)=[CH:18][N:17]=[C:16]([S:21][CH3:22])[N:15]=1)=[O:13].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl.[Cu]I.CN(C)C=O>[CH3:10][O:11][C:12]([C:14]1[C:19]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[CH3:9])=[CH:18][N:17]=[C:16]([S:21][CH3:22])[N:15]=1)=[O:13]

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 1365982-MethylphenylacetyleneHCID 2794729Methyl 5-bromo-2-(methylsulfanyl)pyrimidine-4-carboxylate

Produkt 1

HCID 575569302-Methylsulfanyl-5-(2-methylphenyl)ethynylpyrimidine-4-carboxylic acid methyl esterAusbeute 79,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 1-ethynyl-2-methylbenzene (0.53 g, 4.6 mmol), 5-bromo-2-methylsulfanylpyrimidine-4-carboxylic acid methyl ester (11.0 g, 3.8 mmol), triethylamine (2.5 ml), triphenylphosphine (0.125 g, 0.48 mmol), copper (I) iodide (0.025 g, 0.13 mmol), bistriphenyphosphinepalladium (II) dichloride (0.10 g, 0.14 mmol) and dimethylformamide (1 ml) was stirred in a heavy-walled Smith process vial and irradiated with microwaves to maintain 100° C. for 20 min. The cooled mixture was diluted with dichloromethane (20 ml) and washed with 5% hydrochloric acid (20 ml), water (20 ml), saturated aqueous sodium hydrogencarbonate solution (20 ml) and water (20 ml) then dried (MgSO4) and evaporated in vacuo. The residual oil was purified by flash column chromatography over silica using a 1:4 mixture of hexane and dichloromethane as eluant. Appropriate fractions were combined and the solvents removed in vacuo to give 2-methylsulfanyl-5-(2-methylphenyl)ethynylpyrimidine-4-carboxylic acid methyl ester (0.9 g) as an orange oil. 250 MHz 1H-NMR (CDCl3) δ (ppm): 2.45 (s, 3H) (ArCH3), 2.55 (s, 3H) (—SCH3), 3.95 (s, 3H)(CO2CH3), 7.05-7.25 (m, 3H) (3×ArH), 7.45 (m, 1H) (ArH), 8.7 (s, 1H) (ArH); m/z (M+H)+. 299, HPLC purity 96%, HPLC retention time 4.15 min.

Aufarbeitung

  1. customirradiated with microwaves
  2. washwashed with 5% hydrochloric acid (20 ml), water (20 ml), saturated aqueous sodium hydrogencarbonate solution (20 ml) and water (20 ml)
  3. dry with materialthen dried (MgSO4)
  4. customevaporated in vacuo
  5. customThe residual oil was purified by flash column chromatography over silica using
  6. additiona 1:4 mixture of hexane and dichloromethane as eluant
  7. customthe solvents removed in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-e38bbfabaef245b2831e4ffd888e6c61
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08058283B2

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