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 1476407Notes

Reaction equation

HRID 1476407 reaction equation
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

Participants

8

Reactant 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

Product 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

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-54166b2ff82c4908a7e8334baaf4ad0b
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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