2-Chloro-6-methylpyrazine → HCID 71536681, Verbindung

HRID 1503269Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1503269
[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[C:5]([NH:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][C:10]([C:18]#[CH:19])([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:6].Cl[C:24]1[CH:29]=[N:28][CH:27]=[C:26]([CH3:30])[N:25]=1>C(N(CC)CC)C.C(#N)C.C(OCC)(=O)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>[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[C:5]([NH:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][C:10]([C:18]#[C:19][C:24]4[CH:29]=[N:28][CH:27]=[C:26]([CH3:30])[N:25]=4)([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:6]

Komponenten

8

Edukt 2

HCID 71700952-Chloro-6-methylpyrazineHCID 117702457HCID 117702457, Verbindung

Produkt 1

HCID 71536681HCID 71536681, VerbindungAusbeute 38,9 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6342AcetonitrileLösungsmittelHCID 8471TriethylamineLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To a stirred mixture of intermediate 8, 3-chloro-N-(3-ethynyl-adamantan-1-yl)-benzamide (60 mg, 0.19 mmol) and 2-chloro-6-methylpyrazine (60 mg, 0.47 mmol) in triethylamine (0.5 mL) and acetonitrile (2 mL) was added Pd(PPh3)4 (3 mg, 0.02 mmol), followed by an addition of CuI (3 mg, 0.016 mmol). After heated at 70° C. for three hours, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (30 mL), washed with water (50 mL) and brine, dried over Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by Prep HPLC to give 30 mg (38%) of the title compound, 3-chloro-N-[3-(6-methyl-pyrazin-2-ylethynyl)-adamantan-1-yl]-benzamide. 1H NMR (500 MHz, CDCl3): δ 8.57 (brs, 1H), 7.69 (t, J=2.0 Hz, 1H), 7.59 (d, J=8.0 Hz, 1H), 7.45 (d, J=8.0 Hz, 1H), 7.35 (t, J=8.0 Hz, 1H), 5.78 (s, 1H), 2.57 (s, 3H), 2.40 (s, 2H), 2.25 (s, 2H), 2.17-2.15 (m, 2H), 2.06-1.96 (m, 6H), 1.73-1.70 (m, 2H); ESI-MS m/z: 406 (M+H)+.

Aufarbeitung

  1. temperaturethe reaction mixture was cooled to room temperature
  2. washwashed with water (50 mL) and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by Prep HPLC

Quellen und Nachweise

ORD-Eintrag
ord-254246cb506448babd87e54e5031f5b5
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09212165B2

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