Sodium Carbonate → [3-Amino-6-(1h-indol-5-yl)-pyrazin-2-yl]-pyridin-3-yl-methanone

HRID 2387188

반응식

HRID 2387188 반응식
C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:31][C:32]1[C:33]([C:39]([C:41]2[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=2)=[O:40])=[N:34][C:35](Br)=[CH:36][N:37]=1.B(O)(O)[C:48]1[NH:56][C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:49]=1.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O.C([O-])(O)=O.[Na+].C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.C(O)C>[NH2:31][C:32]1[C:33]([C:39]([C:41]2[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=2)=[O:40])=[N:34][C:35]([C:52]2[CH:51]=[C:50]3[C:55](=[CH:54][CH:53]=2)[NH:56][CH:48]=[CH:49]3)=[CH:36][N:37]=1

참가 물질

9

반응물 4

HCID 10340Sodium CarbonateHCID 821241,4-Bis(diphenylphosphino)butaneHCID 225673581H-Indol-2-ylboronic acidHCID 86634541(3-Amino-6-bromo-pyrazin-2-yl)-pyridin-3-yl-methanone

생성물 1

HCID 44233093[3-Amino-6-(1h-indol-5-yl)-pyrazin-2-yl]-pyridin-3-yl-methanone

시약·촉매·용매 4

HCID 498840Bis(benzonitrile)palladium chloride촉매HCID 702Ethanol용매HCID 8857Ethyl Acetate용매HCID 516892Sodium Bicarbonate용매

실험 절차

Bis(benzonitrile)palladium(II)chloride (5.2 mg, 0.013 mmol) and 1,4-bis(diphenylphosphino)butane (6.7 mg, 0.015 mmol) in toleune (0.6 ml) are stirred for 20 minutes. (3-Amino-6-bromo-pyrazin-2-yl)-pyridin-3-yl-methanone (Intermediate AA) (0.075 g, 0.27 mmol), 5-indoylboronic acid (0.056 g, 0.35 mmol), ethanol (0.36 ml) and 1M Na2CO3 (0.65 ml) are added and the reaction is heated using microwave radiation at 140° C. for 20 minutes. The mixture is diluted with EtOAc and sat. aq. NaHCO3. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic extracts are dried (MgSO4), and purified by preperative HPLC (0-100% MeCN in water −0.1% TFA) to yield the title compound as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ 11.27 (1H, s), 9.21 (1H, s), 9.09 (1H, s), 8.86 (1H, dd), 8.39-8.41 (1H, dt), 8.19 (1H, s), 7.99 (2H, s), 7.65-7.73 (2H, m), 7.5 (1H, d), 7.44 (1H, t), 6.53 (1H, s). MS m/z 316 [M+H]+

후처리

  1. temperaturethe reaction is heated
  2. customat 140° C.
  3. customfor 20 minutes
  4. customThe layers are separated
  5. extractionthe aqueous layer is extracted with EtOAc
  6. dry with materialThe combined organic extracts are dried (MgSO4)
  7. custompurified by preperative HPLC (0-100% MeCN in water −0.1% TFA)

출처 및 근거

ORD 기록
ord-927d1354443e4164a44001ee57b48804
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08268834B2

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