Potassium Carbonate → 1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-4-nitro-1H-indazole

HRID 706537Notes

Reaction equation

HRID 706537 reaction equation
O1[CH2:6][CH2:5]OCC1.BrC1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[N+:17]([O-:19])=[O:18])[N:10]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]([CH3:29])[CH3:28])[N:22]=2)[N:9]=1.CB(O)O.C(=O)([O-])[O-].[K+].[K+]>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:27]([C:23]1[N:22]=[C:21]([CH2:20][N:10]2[C:11]3[C:16](=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][CH:12]=3)[C:5]([CH3:6])=[N:9]2)[CH:26]=[CH:25][CH:24]=1)([CH3:29])[CH3:28]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 139377Methylboronic Acid2×HCID 679758823-bromo-1-((6-isopropylpyridin-2-yl)methyl)-4-nitro-1H-indazole

Product 1

HCID 679762021-((6-isopropylpyridin-2-yl)methyl)-3-methyl-4-nitro-1H-indazoleYield 73%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
120 °C

Procedure

A 3 liter heavy walled reaction flask was charged with dioxane (1 liter), 3-bromo-1-((6-isopropylpyridin-2-yl)methyl)-4-nitro-1H-indazole (90 g, 0.24 mol), methyl boronic acid (72 g, 1.20 mol), Pd(PPh3)4 (9.7 g, 0.0084 mol), potassium carbonate (99.5 g, 0.719 mol), followed by 200 mL of water. This mixture was purged with argon for 10 minutes, flask sealed and heated to 120° C. for 16 hours. Another 1.5 mol % of Pd(PPh3)4 was added followed by another 2 equivalents of methyl boronic acid, and the mixture warmed to 120° C. for 24 hours. The mixture was diluted with water and extracted with EtOAc. The combined organic extracts were dried over sodium sulfate and concentrated. Column chromatography (5% ethyl acetate/hexane to 10% ethyl acetate/hexane) gave 54 g (73%) of 1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-4-nitro-1H-indazole as an orange/yellow solid.

Workup

  1. customThis mixture was purged with argon for 10 minutes
  2. customflask sealed
  3. additionAnother 1.5 mol % of Pd(PPh3)4 was added
  4. temperaturethe mixture warmed to 120° C. for 24 hours
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-68ba87c1860c4ec78574a717269daca9
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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