Sodium Carbonate → HCID 68159279, compound

HRID 508197Notes

Reaction equation

HRID 508197 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4](C(OC(C)(C)C)=O)[N:3]=1.[CH3:18][O:19][C:20]1[CH:46]=[CH:45][C:23]([CH2:24][N:25]2[C:29]([C:30]3[CH:35]=[CH:34][C:33](B4OC(C)(C)C(C)(C)O4)=[CH:32][CH:31]=3)=[N:28][N:27]=[N:26]2)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>FC(F)(F)C(C1C=CC(C2C3C(=CC=CC=3)N(S(C3C=CC=CC=3C(F)(F)F)(=O)=O)N=2)=CC=1)(O)C(F)(F)F.O1CCOCC1.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>[CH3:18][O:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:24][N:25]2[C:29]([C:30]3[CH:35]=[CH:34][C:33]([C:2]4[C:10]5[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=5)[NH:4][N:3]=4)=[CH:32][CH:31]=3)=[N:28][N:27]=[N:26]2)=[CH:45][CH:46]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 57506738HCID 57506738, compoundHCID 69020451HCID 69020451, compound

Product 1

HCID 68159279HCID 68159279, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolventHCID 60162681HCID 60162681, compoundSolvent

Procedure

Tert-butyl 3-bromo-1H-indazole-1-carboxylate (5.0 g, 16.8 mmol) and a mixture of the regio-isomers of 1-(4-methoxybenzyl)-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-tetrazole (Example 19, step ii) (7.92 g, 20.2 mmol) were dissolved in 100 ml of a 1 to 1 mixture of 1,4-dioxane and water under a nitrogen atmosphere. Sodium carbonate (5.35 g, 50.5 mmol) was added and the system was purged with nitrogen. Then Pd(PPh3)4 (486 mg, 0.42 mmol) was added and the reaction mixture was heated overnight at reflux temperature under a nitrogen atmosphere. After cooling to room temperature the mixture was diluted with water and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over magnesium sulfate. After filtration the solvent was removed under reduced pressure. The residue was purified on SiO2 using 20 to 30% ethyl acetate in hexane as the eluent to give 3-(4-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)phenyl)-1H-indazole as a mixture of two regioisomers in a 2 to 1 ratio (2.8 g) as a white solid.

Workup

  1. customthe system was purged with nitrogen
  2. temperaturethe reaction mixture was heated overnight
  3. temperatureat reflux temperature under a nitrogen atmosphere
  4. extractionextracted with ethyl acetate
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationAfter filtration the solvent
  8. customwas removed under reduced pressure
  9. customThe residue was purified on SiO2 using 20 to 30% ethyl acetate in hexane as the eluent

Sources & evidence

ORD record
ord-82bf09028f5f412591a7c0a3d44be414
Source dataset
uspto-grants-2015_08
Patent number
US09095583B2

Reaction notes

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