Hydrochloric Acid → HCID 86698814, compound

HRID 338478Notes

Reaction equation

HRID 338478 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][CH2:6][CH2:5]2.CC1(C)COB(B2OCC(C)(C)CO2)OC1.C([O-])(=O)C.[K+].Br[C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][C:41]=1[Cl:42])[NH:38][N:37]=[C:36]2[C:43]([OH:45])=[O:44].C(=O)([O-])[O-].[K+].[K+].Cl>O1CCOCC1.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].O.CCO>[Cl:42][C:41]1[CH:40]=[C:39]2[C:35]([C:36]([C:43]([OH:45])=[O:44])=[N:37][NH:38]2)=[CH:34][C:33]=1[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][CH2:6][CH2:5]2

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2671395-bromo-2,3-dihydro-1H-indeneHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 866987915-bromo-6-chloro-1H-indazole-3-carboxylic acid

Product 1

HCID 86698814HCID 86698814, compoundYield 6%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 702EthanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A suspension of 5-bromoindane (100.0 mg, 0.51 mmol), 5,5,5′,5′-tetramethyl-2,2′-bi-1,3,2-dioxaborinane (191 mg, 0.56 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (42.0 mg, 0.025 mmol) and potassium acetate (150 mg, 1.50 mmol) in 1,4-dioxane (1 mL) was sealed in a pressure tube and heated to 130° C. for 1 hour. To this mixture was added 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (100 mg, 0.36 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (14.7 mg, 0.018 mmol), 2N aqueous potassium carbonate solution (0.5 mL, 1.0 mmol) and EtOH (2 mL). The reaction mixture was sealed and heated to 130° C. for 1 hour. Water (3 mL) was added to the reaction mixture, followed by 1N HCl solution to adjust the pH to 2. The layers were separated and the aqueous layer was extracted with EtOAc (3×5 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by reverse phase HPLC (Column: Waters XBridge C18 19×100 mm, 5 μm; Mobile phase A: 0.03% NH4OH in water (v/v); Mobile phase B: 0.03% NH4OH in MeCN (v/v); 80.0% H2O/20.0% MeCN linear to 70.0% H2O/30.0% MeCN in 8.5 min, 70.0% H2O/30.0% MeCN linear to 0% H2O/100% MeCN in 0.5 min HOLD at 0% H2O/100% MeCN from 9.0 to 10.0 min. Flow: 25 mL/min) to afford the title compound (6.2 mg, 6% yield). MS (ES+) 313.1 (M+H)+. Retention time=3.11 minutes (Column: Waters Atlantis dC18 4.6×50 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); Gradient: 95:5 A:B linear to 5:95 A:B in 4.0 min, hold at 5:95 A:B to 5.0 min. Flow: 2 mL/min).

Workup

  1. customwas sealed in a pressure tube
  2. customThe reaction mixture was sealed
  3. temperatureheated to 130° C. for 1 hour
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (3×5 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by reverse phase HPLC (Column: Waters XBridge C18 19×100 mm, 5 μm; Mobile phase A: 0.03% NH4OH in water (v/v); Mobile phase B: 0.03% NH4OH in MeCN (v/v); 80.0% H2O/20.0% MeCN linear to 70.0% H2O/30.0% MeCN in 8.5 min, 70.0% H2O/30.0% MeCN linear to 0% H2O/100% MeCN in 0.5 min HOLD at 0% H2O/100% MeCN from 9.0 to 10.0 min. Flow: 25 mL/min)

Sources & evidence

ORD record
ord-663deb1930ce449fb552fb0519f32502
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

Loading…