Triethylamine → HCID 71229923, Verbindung

HRID 1485162

Reaktionsgleichung

Reaktionsgleichung von HRID 1485162
[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][CH:12]=1)[C:6]([O:8][CH3:9])=[O:7])#[CH:2].C(N(CC)CC)C.Cl[C:21]1[C:26]([C:27]([F:30])([F:29])[F:28])=[CH:25][N:24]=[C:23]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([N:38]3[CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40][CH2:39]3)=[CH:34][CH:33]=2)[N:22]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:9][O:8][C:6]([C:5]1[CH:4]=[C:3]([C:1]#[C:2][C:25]2[C:26]([C:27]([F:29])([F:28])[F:30])=[CH:21][N:22]=[C:23]([NH:31][C:32]3[CH:33]=[CH:34][C:35]([N:38]4[CH2:39][CH2:40][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:42][CH2:43]4)=[CH:36][CH:37]=3)[N:24]=2)[CH:12]=[CH:11][CH:10]=1)=[O:7]

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 112751593-Ethynylbenzoic acid methyl esterHCID 86675713HCID 86675713, Verbindung

Produkt 1

HCID 71229923HCID 71229923, VerbindungAusbeute 57,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a nitrogen de-gassed solution of methyl 3-ethynylbenzoate (I31) (0.105 g, 0.655 mmol) in dry DMF (6 mL) were added triethylamine (0.308 mL, 2.18 mmol) followed by tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I3) (0.250 g, 0.546 mmol), triphenylphosphine (0.021 g, 0.082 mmol), trans-dichlorobis(triphenylphosphine)palladium(II) (0.038 g, 0.055 mmol) and Cu(I)I (0.016 g, 0.082 mmol). The reaction mixture was heated under microwave irradiation at 120° C. for 20 minutes, concentrated to dryness in vacuo and purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.) to give the title compound (I32) (0.182 g, 57% yield) as an orange solid; 1H NMR (400 MHz, d6-DMSO) δ 10.28 (brs, 1H), 8.78 (s, 1H), 8.16-8.03 (m, 2H), 7.90 (d, J=7.8 Hz, 1H), 7.69 (t, J=7.9 Hz, 1H), 7.55 (d, J=9.0 Hz, 2H), 6.96 (d, J=9.0 Hz, 2H), 3.90 (s, 3H), 3.50-3.41 (m, 4H), 3.11-2.99 (m, 4H), 1.42 (s, 9H). LCMS Method C: rt 6.82 min; m/z 582.2 [M+H]+.

Aufarbeitung

  1. concentrationconcentrated to dryness in vacuo
  2. custompurified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.)

Quellen und Nachweise

ORD-Eintrag
ord-6c3cc74ae4b446978088b5aab0b722a7
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09421205B2

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