1,4-Dioxane → HCID 178425143、化合物

HRID 475977ノート

反応式

HRID 475977 の反応式
Cl[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[CH3:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34](B3OC(C)(C)C(C)(C)O3)[CH:35]=2)[N:30](C(OC(C)(C)C)=O)[N:29]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>CCOC(C)=O.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].C(Cl)Cl.O>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([C:34]2[CH:35]=[C:36]3[C:31](=[CH:32][CH:33]=2)[NH:30][N:29]=[C:28]3[CH3:27])[CH:3]=1)=[O:15]

参加物

8

反応物 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 565974256-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamideHCID 57415707tert-Butyl 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-1-carboxylate

生成物 1

HCID 178425143HCID 178425143、化合物

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
105 °C

実験手順

To a 10 mL microwave vial were sequentially added 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (0.12 g, 0.321 mmol), 1,1-dimethylethyl 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-1-carboxylate (0.138 g, 0.385 mmol), potassium phosphate (tribasic) (0.204 g, 0.963 mmol), 1,4-dioxane (3 mL), and water (0.75 mL). The stirring suspension was degassed with nitrogen for 10 min., wherein an emulsion had formed. Next added PdCl2(dppf)-CH2Cl2 adduct (0.039 g, 0.048 mmol) and the contents were placed onto a heat block and stirred at 105° C. overnight. After cooling to room temperature, the reaction mixture was diluted with EtOAc and filtered through Celite. The filter pad was washed with 50% THF/EtOAc. Silica gel was added to the combined filtrates and the mixture concentrated in vacuo to a solid. The contents were purified by silica gel chromatography (dry loaded, eluent: 5-80% gradient of DCM and chloroform containing 10% 2M Ammonia (in methanol)). The isolated solid was dried in vacuum oven at 45° C. overnight to afford the final product as 0.126 g (81%). LCMS E-S (M+H)=470.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.56 (d, J=6.57 Hz, 6H), 2.13 (s, 3H), 2.25 (s, 3H), 2.60 (s, 3H), 4.43 (d, J=5.05 Hz, 2H), 5.31-5.43 (m, 1H), 5.91 (s, 1H), 7.60 (d, J=8.84 Hz, 1H), 8.22 (s, 1H), 8.29-8.37 (m, 2H), 8.60 (s, 1H), 8.97 (t, J=5.05 Hz, 1H), 11.58 (br. s., 1H), 12.84 (s, 1H).

後処理

  1. customThe stirring suspension was degassed with nitrogen for 10 min.
  2. customwherein an emulsion had formed
  3. temperatureAfter cooling to room temperature
  4. filtrationfiltered through Celite
  5. washThe filter pad was washed with 50% THF/EtOAc
  6. additionSilica gel was added to the combined filtrates
  7. concentrationthe mixture concentrated in vacuo to a solid
  8. customThe contents were purified by silica gel chromatography (dry loaded, eluent: 5-80% gradient of DCM and chloroform containing 10% 2M Ammonia (in methanol))
  9. customThe isolated solid was dried in vacuum oven at 45° C. overnight

出典と根拠

ORDレコード
ord-5b5c261afee243028eef68747d689cee
出典データセット
uspto-grants-2014_01
特許番号
US08637509B2

反応ノート

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