Sodium Carbonate → HCID 86715493, compound

HRID 2284586Notes

Reaction equation

HRID 2284586 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH:9]=[C:10]3[C:14](=[C:15]([C:17]([O:19][CH3:20])=[O:18])[CH:16]=2)[NH:13][N:12]=[CH:11]3)=[CH:6][CH:5]=[CH:4][N:3]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][C:23]=1[CH3:31].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:2]2[C:7]([C:8]3[CH:9]=[C:10]4[C:14](=[C:15]([C:17]([O:19][CH3:20])=[O:18])[CH:16]=3)[NH:13][N:12]=[CH:11]4)=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:24][C:23]=1[CH3:31]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2774580(4-Fluoro-3-methylphenyl)boronic acidHCID 86715494HCID 86715494, compound

Product 1

HCID 86715493HCID 86715493, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A single necked round bottom flask (100 mL) equipped with a magnetic stirring bar was charged with methyl 5-(2-chloropyridin-3-yl)-1H-indazole-7-carboxylate (0.88 g, 3.0 mmol), 4-fluoro-3-methylphenyl boronic acid (0.56 g, 3.63 mmol), PdCl2(PPh3)4 (214 mg g, 1.0 mmol), 1,4-dioxane (75 mL) and 2M aq. Na2CO3 (4.2 mL, 8.4 mmol mL) under argon atmosphere. The rubber septum was replaced with reflux condenser containing three-way stopcock. The system was then evacuated three times and back filled with argon and externally heated at 100° C. (oil bath) for 48 h. The heterogeneous reaction mixture was allowed to cool to room temperature and concentrated under vacuum to remove the volatiles by rotary evaporator. The crude concentrate flask was charged with chloroform (100 mL)/water (30 mL) and stirred. Organic layer was separated and the aqueous layer further extracted with chloroform (75 mL). Combined organic layers were stirred over MgSO4/Celite® for 20 min, suction filtered and filter cake washed with chloroform (30 mL). The filtrate collected was concentrated and purified by silica gel flash chromatography [Combiflash® companion System® with RediSep® silica gel column (24g), solvent eluent gradient 30-50% EtOAc/hexanes] to obtain methyl 5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-1H-indazole-7-carboxylate (420 mg, 39%) as a white solid. 1H NMR (DMSO-d6): δ 13.1 (s, 1H), 8.62 (dd, 1H, J=0.5 and 4.7 Hz), 8.04 (s, 1H), 7.83 (d, 1H, J=7.6 Hz), 7.66 (s, 1H), 7.45-7.34 (app m, 3H), 7.02 (d, 1H, J=8.5 Hz), 6.96-6.85 (m, 2H), 2.11 (s, 3H). 19F NMR (DMSO-d6): δ −118.91. LCMS: rt 5.23 min (A), purity 93%,MS (m/e) 362 (MH+).

Workup

  1. customA single necked round bottom flask (100 mL) equipped with a magnetic stirring bar
  2. temperaturewith reflux condenser
  3. additioncontaining three-way stopcock
  4. customThe system was then evacuated three times
  5. additionback filled with argon
  6. temperatureto cool to room temperature
  7. concentrationconcentrated under vacuum
  8. customto remove the volatiles
  9. customby rotary evaporator
  10. concentrationThe crude concentrate flask
  11. additionwas charged with chloroform (100 mL)/water (30 mL)
  12. customOrganic layer was separated
  13. extractionthe aqueous layer further extracted with chloroform (75 mL)
  14. stirringCombined organic layers were stirred over MgSO4/Celite® for 20 min
  15. filtrationsuction filtered
  16. filtrationfilter cake
  17. washwashed with chloroform (30 mL)
  18. customThe filtrate collected
  19. concentrationwas concentrated
  20. custompurified by silica gel flash chromatography [Combiflash® companion System® with RediSep® silica gel column (24g), solvent eluent gradient 30-50% EtOAc/hexanes]

Sources & evidence

ORD record
ord-bc0de956f4ce48538e80932ab683d852
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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