Sodium Carbonate → N-((1,2-dihydro-6-methyl-2-oxo-4-propylpyridin-3-yl)methyl)-1-isopropyl-6-(thiophen-3-yl)-1H-indazole-4-carboxamide

HRID 1476407ノート

反応式

HRID 1476407 の反応式
Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:28])[NH:20][C:21]([CH3:27])=[CH:22][C:23]=2[CH2:24][CH2:25][CH3:26])=[O:15])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.CC1(C)C(C)(C)OB([C:37]2[CH:41]=[CH:40][S:39][CH:38]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.O.C([O-])(O)=O.[Na+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:27][C:21]1[NH:20][C:19](=[O:28])[C:18]([CH2:17][NH:16][C:14]([C:4]2[C:5]3[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=3[CH:10]=[C:2]([C:37]3[CH:41]=[CH:40][S:39][CH:38]=3)[CH:3]=2)=[O:15])=[C:23]([CH2:24][CH2:25][CH3:26])[CH:22]=1

参加物

8

反応物 3

HCID 10340Sodium CarbonateHCID 27605974,4,5,5-Tetramethyl-2-(thiophen-3-yl)-1,3,2-dioxaborolaneHCID 674653266-bromo-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide

生成物 1

HCID 54596916N-((1,2-dihydro-6-methyl-2-oxo-4-propylpyridin-3-yl)methyl)-1-isopropyl-6-(thiophen-3-yl)-1H-indazole-4-carboxamide

試薬・触媒・溶媒 4

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

To a stirred solution of 6-bromo-N-((1,2-dihydro-6-methyl-2-oxo-4-propylpyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide (0.2 g, 0.44 mmol) in DMF (10 mL) was added 4,4,5,5-tetramethyl-2-(thiophen-3-yl)-1,3,2-dioxaborolane (0.113 g, 0.53 mmol) followed by PdCl2(PPh3)2 (0.06 g, 0.08 mmol) and the reaction mixture was stirred for 5 min. Sodium carbonate (0.119 g, 0.940 mmol) dissolved in water (2 mL) was added and the contents were stirred at 120° C. for 3 h. The reaction mixture was diluted with NaHCO3 solution and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine solution (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford the crude product. The crude product was purified by silica gel chromatography (eluent: 4% MeOH\EtOAc) to afford the title compound as an off white solid (75 mg, 38%). 1H NMR (DMSO-d6, 400 MHz): δ 0.883 (t, J=7.2 Hz, 3H), 1.491-1.550 (m, 8H), 2.13 (s, 3H), 2.501 (s, 2H), 4.419 (d, J=3.6 Hz, 2H), 5.130 (t, J=6.4 Hz, 1H), 5.912 (s, 1H), 7.691 (s, 1H), 7.766 (d, J=4.4 Hz, 1H), 7.930 (s, 1H), 8.041 (s, 1H), 8.171 (s, 1H), 8.353 (s, 1H), 8.563 (s, 1H), 11.530 (s, 1H). LCMS (ES+) m/z: 449.09.

後処理

  1. additionwas added
  2. stirringthe contents were stirred at 120° C. for 3 h
  3. extractionextracted with ethyl acetate (3×20 mL)
  4. washThe combined organic layers were washed with brine solution (20 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford the crude product
  9. customThe crude product was purified by silica gel chromatography (eluent: 4% MeOH\EtOAc)

出典と根拠

ORDレコード
ord-54166b2ff82c4908a7e8334baaf4ad0b
出典データセット
uspto-grants-2015_04
特許番号
US09018382B2

反応ノート

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