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 520650ノート

反応式

HRID 520650 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

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

反応条件

温度
140 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-4a0e8f73252242b0b3255c51df8f760e
出典データセット
uspto-grants-2016_05
特許番号
US09326987B2

反応ノート

読み込み中…