Sodium Carbonate → 2-Methyl-N-[6-(2-oxo-2,3-dihydro-1H-indol-4-yl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

HRID 520650노트

반응식

HRID 520650 반응식
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5](Cl)[NH:6]2.[CH3:12][C:13]1[S:14][CH:15]=[C:16]([C:18]([NH:20][C:21]2[C:22]3[C:26]([CH:27]=[C:28](B4OC(C)(C)CC(C)(C)O4)[CH:29]=2)=[N:25][N:24](C2CCCCO2)[CH:23]=3)=[O:19])[N:17]=1.C(=O)([O-])[O-:47].[Na+].[Na+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH3:12][C:13]1[S:14][CH:15]=[C:16]([C:18]([NH:20][C:21]2[CH:29]=[C:28]([C:2]3[CH:10]=[CH:9][CH:8]=[C:7]4[C:3]=3[CH2:4][C:5](=[O:47])[NH:6]4)[CH:27]=[C:26]3[C:22]=2[CH:23]=[N:24][NH:25]3)=[O:19])[N:17]=1

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 197003094-bromo-2-chloro-1H-indoleHCID 582558332-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide

생성물 1

HCID 532332132-Methyl-N-[6-(2-oxo-2,3-dihydro-1H-indol-4-yl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매

반응 조건

온도
140 °C

실험 절차

4-Bromo-2-chloro-1H-indole (24 mg), 2-methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide (50 mg), Pd(dppf)Cl2 (8 mg) and sodium carbonate (44 mg) were added to a microwave vial. 1,4-Dioxane (0.5 ml) and water (0.5 ml) were added and the reaction was heated in the microwave at 140° C. for 20 min. The reaction was passed through a 1 g silica cartridge washing with DCM:methanol. The solvent was evaporated in the blow down. The residue was dissolved in DMSO:methanol (1.6 ml, 1:1, v/v), passed through a C18 cartridge (1 g) washing with acetonitrile and evaporated in the blow down. The residue was dissolved in DMSO:methanol (1.6 ml, 1:1, v/v) and purified by MDAP (method M). The pure fraction was evaporated to dryness to give title compound, 8 mg.

후처리

  1. washwashing with DCM
  2. customThe solvent was evaporated in the blow down
  3. dissolutionThe residue was dissolved in DMSO
  4. washwashing with acetonitrile
  5. customevaporated in the blow down
  6. dissolutionThe residue was dissolved in DMSO
  7. custommethanol (1.6 ml, 1:1, v/v) and purified by MDAP (method M)
  8. customThe pure fraction was evaporated to dryness

출처 및 근거

ORD 기록
ord-4a0e8f73252242b0b3255c51df8f760e
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09326987B2

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