Sodium Carbonate → N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(4-methylpiperazin-1-yl)pyridin-2-yl)-1H-indazole-4-carboxamide

HRID 85493Notes

Reaction equation

HRID 85493 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=2[CH3:25])=[O:16])[C:5]2[C:6]([CH3:14])=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[CH3:28][N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:40]=[C:39](B3OC(C)(C)C(C)(C)O3)[CH:38]=[CH:37][N:36]=2)[CH2:31][CH2:30]1.C([O-])([O-])=O.[Na+].[Na+]>O.CN(C=O)C.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>[CH3:25][C:24]1[CH:23]=[C:22]([CH3:26])[NH:21][C:20](=[O:27])[C:19]=1[CH2:18][NH:17][C:15]([C:4]1[C:5]2[C:6]([CH3:14])=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=[C:2]([C:37]2[CH:38]=[CH:39][CH:40]=[C:35]([N:32]3[CH2:31][CH2:30][N:29]([CH3:28])[CH2:34][CH2:33]3)[N:36]=2)[CH:3]=1)=[O:16]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27695372-(4-Methylpiperazin-1-yl)pyridine-4-boronic acid, pinacol esterHCID 545962226-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indazole-4-carboxamide

Product 1

HCID 54596368N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(4-methylpiperazin-1-yl)pyridin-2-yl)-1H-indazole-4-carboxamideYield 32%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A stirred solution of 6-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indazole-4-carboxamide, 3 (200 mg, 0.464 mmol), 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine (154 mg, 0.510 mmol) and Na2CO3 (123 mg, 1.160 mmol) in a mixture of water (3 mL) and DMF (15 mL) was degassed with argon gas for 30 min. Then PdCl2(PPh3)2 (16.28 mg, 0.023 mmol) was added and heated to 120° C. for 3 h. Then the reaction mixture was filtered through Celite bed and the Celite bed was washed with ice cold water (2×100 mL). The filtrate was extracted with EtOAc (20 mL), dried over anhydrous sodium sulphate, filtered, and concentrated to afford 150 mg of crude product. The crude product was purified by silica gel chromatography over (eluent: 5% MeOH/DCM) to afford the title compound as an off-white solid (85 mg, 32%). 1HNMR (DMSO-d6, 400 MHz): 0.889 (t, J=14.4 Hz, 3H), 1.554-1.483 (m, 8H), 2.134 (s, 3H), 2.55 (s, 3H), 4.411 (d, J=1.6 Hz, 2H), 5.059 (m, 1H), 5.913 (s, 1H), 7.830 (s, 1H), 8.047 (s, 1H), 8.08 (s, 1H), 8.306 (s, 1H), 8.462 (s, 1H), 11.53 (s, 1H), 13 (brs, 1H). LCMS (ES+) m/z=528.2.

Workup

  1. customwas degassed with argon gas for 30 min
  2. filtrationThen the reaction mixture was filtered through Celite bed
  3. washthe Celite bed was washed with ice cold water (2×100 mL)
  4. extractionThe filtrate was extracted with EtOAc (20 mL)
  5. dry with materialdried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford 150 mg of crude product
  9. customThe crude product was purified by silica gel chromatography over (eluent: 5% MeOH/DCM)

Sources & evidence

ORD record
ord-03b8ddd247ac4b66ad6ea88958c6f49b
Source dataset
uspto-grants-2014_09
Patent number
US08846935B2

Reaction notes

Loading…