Potassium Carbonate → HCID 86698807, compound

HRID 338471Notes

Reaction equation

HRID 338471 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][N:6]=[C:5]2[C:12]([OH:14])=[O:13].CC1(C)COB([C:22]2[CH:27]=[CH:26][C:25]([C:28]([OH:34])([CH3:33])[C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=2)OC1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CCO.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]>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([C:12]([OH:14])=[O:13])=[N:6][NH:7]2)=[CH:3][C:2]=1[C:22]1[CH:27]=[CH:26][C:25]([C:28]([OH:34])([CH3:33])[C:29]([F:31])([F:32])[F:30])=[CH:24][CH:23]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 866987915-bromo-6-chloro-1H-indazole-3-carboxylic acidHCID 86698806HCID 86698806, compound

Product 1

HCID 86698807HCID 86698807, compoundYield 15.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (30.0 mg, 0.11 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (7.3 mg, 0.010 mmol) was purged with N2. To this mixture was added 2-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-phenyl]-1,1,1-trifluoropropan-2-ol (35.0 mg, 0.12 mmol) in toluene (1.0 mL) and EtOH (0.5 mL), followed by 2N aqueous potassium carbonate solution (0.22 mL, 0.44 mmol). The reaction mixture was heated to 110° C. for 18 hours, cooled to room temperature and concentrated in vacuo. The resulting solid was partitioned between water and EtOAc, and acidified to pH 5 with aqueous 1N citric acid. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by reverse phase HPLC (Column: Waters Sunfire C18 19×100 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); HOLD at 100.0% H2O/0.0% MeCN for 1.0 min. 100.0% H2O/0.0% MeCN linear to 5.0% H2O/95.0% MeCN in 6.75 min, linear to 0% H2O/100% MeCN to 7.0 min. HOLD at 0% H2O/100% MeCN from 7.0 to 8.0 min. Flow: 30 mL/min) to give the title compound (6.5 mg, 15% yield).

Workup

  1. customwas purged with N2
  2. temperaturecooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customThe resulting solid was partitioned between water and EtOAc
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by reverse phase HPLC (Column: Waters Sunfire C18 19×100 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); HOLD at 100.0% H2O/0.0% MeCN for 1.0 min. 100.0% H2O/0.0% MeCN linear to 5.0% H2O/95.0% MeCN in 6.75 min, linear to 0% H2O/100% MeCN to 7.0 min. HOLD at 0% H2O/100% MeCN from 7.0 to 8.0 min. Flow: 30 mL/min)

Sources & evidence

ORD record
ord-25c966ad8d624bd39c54bd390d8b5c36
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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