Sodium Bicarbonate → methyl 1-isopropyl-3-methyl-6-(pyridin-3-yl)-1H-indazole-4-carboxylate

HRID 1476459Notes

Reaction equation

HRID 1476459 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:15]([O:17][CH3:18])=[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.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)O1.C(=O)(O)[O-].[Na+]>O1CCOCC1.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>[CH3:14][C:6]1[C:5]2[C:4]([C:15]([O:17][CH3:18])=[O:16])=[CH:3][C:2]([C:27]3[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=3)=[CH:10][C:9]=2[N:8]([CH:11]([CH3:13])[CH3:12])[N:7]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 27346563-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 67466747Methyl 6-bromo-1-isopropyl-3-methyl-1H-indazole-4-carboxylate

Product 1

HCID 67464617methyl 1-isopropyl-3-methyl-6-(pyridin-3-yl)-1H-indazole-4-carboxylateYield 95%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of methyl 6-bromo-1-isopropyl-3-methyl-1H-indazole-4-carboxylate (0.5 g, 1.60 mmol) in 1,4-dioxane (25 mL) was added 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.39 g, 1.92 mmol) followed by PdCl2(dppf)-CH2Cl2 adduct (0.26 g, 0.32 mmol). The reaction mixture was stirred for 5 min, then sodium bicarbonate (0.4 g, 4.80 mmol) dissolved in water (8 mL) was added and the reaction mixture was stirred at 100° C. for 6 h. The reaction mixture was diluted with water and extracted with ethyl acetate (3×40 mL). The combined organic layers were washed with cold water (2×25 mL), brine solution (25 mL), dried over anhydrous Na2SO4, filtered, and concentrated to afford the crude product. The crude compound was purified by silica gel chromatography (eluent: 100% ethyl acetate) to afford the title compound as an off-white solid (470 mg, 94%). 1H NMR (DMSO-d6, 400 MHz): δ 1.485 (d, J=6.4 Hz, 6H), 2.601 (s, 3H), 3.945 (s, 3H), 5.121-5.186 (m, 1H), 7.523-7.554 (m, 1H), 7.902 (s, 1H), 8.232 (d, J=7.6 Hz, 1H), 8.316 (s, 1H), 8.625 (d, J=4 Hz, 1H), 9.045 (s, 1H).

Workup

  1. additionwas added
  2. stirringthe reaction mixture was stirred at 100° C. for 6 h
  3. extractionextracted with ethyl acetate (3×40 mL)
  4. washThe combined organic layers were washed with cold water (2×25 mL), brine solution (25 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford the crude product
  9. customThe crude compound was purified by silica gel chromatography (eluent: 100% ethyl acetate)

Sources & evidence

ORD record
ord-40a55bcbd6e040178d13a3b6a6d8c713
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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