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

HRID 1503267노트

반응식

HRID 1503267 반응식
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

참가 물질

8

반응물 3

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

생성물 1

HCID 71535007Pyrazine-2-carboxylic acid [5-(6-methyl-pyridin-2-ylethynyl)-bicyclo[3.2.1]oct-1-yl]-amide수율 36.1%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

반응 조건

온도
70 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-f43f741af9fa46f8b553f68f6747c0a0
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09212165B2

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