2-Bromo-6-methylpyridine → Pyrazine-2-carboxylic acid [5-(6-methyl-pyridin-2-ylethynyl)-bicyclo[3.2.1]oct-1-yl]-amide

HRID 1503267Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1503267
C1(C(O)=O)CCCC(C(O)=O)C1.[C:13]([C:15]12[CH2:22][C:19]([NH:23][C:24]([C:26]3[CH:31]=[N:30][CH:29]=[CH:28][N:27]=3)=[O:25])([CH2:20][CH2:21]1)[CH2:18][CH2:17][CH2:16]2)#[CH:14].Br[C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([CH3:39])[N:34]=1>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>[CH3:39][C:35]1[N:34]=[C:33]([C:14]#[C:13][C:15]23[CH2:22][C:19]([NH:23][C:24]([C:26]4[CH:31]=[N:30][CH:29]=[CH:28][N:27]=4)=[O:25])([CH2:20][CH2:21]2)[CH2:18][CH2:17][CH2:16]3)[CH:38]=[CH:37][CH:36]=1

Komponenten

8

Edukt 3

HCID 792052-Bromo-6-methylpyridineHCID 1072051,3-Cyclohexanedicarboxylic acidHCID 117702563N-(5-Ethynylbicyclo[3.2.1]octan-1-yl)pyrazine-2-carboxamide

Produkt 1

HCID 71535007Pyrazine-2-carboxylic acid [5-(6-methyl-pyridin-2-ylethynyl)-bicyclo[3.2.1]oct-1-yl]-amideAusbeute 36,1 %

Reagenzien, Katalysatoren, Lösungsmittel 4

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

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To a stirred mixture of intermediate 1, N-(5-ethynylbicyclo[3.2.1]octan-1-yl)pyrazine-2-carboxamide (40 mg, 0.16 mmol) and 2-bromo-6-methylpyridine (30 mg, 0.18 mmol) in TEA (0.5 mL) and acetonitrile (2 mL) was added Pd(PPh3)4 (2 mg, 0.02 mmol), followed by an addition of CuI (4 mg, 0.02 mmol). After heated at 70° C. for three hours, the reaction was cooled to room temperature, diluted with ethyl acetate (30 mL), washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by Prep HPLC to afford 20 mg (36%) of the title compound, pyrazine-2-carboxylic acid [5-(6-methyl-pyridin-2-ylethynyl)-bicyclo[3.2.1]oct-1-yl]-amide, as a white solid. 1HNMR (500 MHz, CDCl3): δ 9.40 (s, 1H), 8.75 (s, 1H), 8.51 (s, 1H), 7.91 (s, 1H), 7.51 (t, J=7.5 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 7.06 (d, J=7.5 Hz, 1H), 2.55-2.52 (m, 4H), 2.29-1.76 (m, 11H); ESI-MS m/z: 347 (M+H)+.

Aufarbeitung

  1. temperaturethe reaction was cooled to room temperature
  2. washwashed with water 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-f43f741af9fa46f8b553f68f6747c0a0
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09212165B2

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