Hydrochloric Acid → HCID 67974881, compound

HRID 2201463Notes

Reaction equation

HRID 2201463 reaction equation
Cl[C:2]1[C:11]([C:12]([F:15])([F:14])[F:13])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:16][CH3:17])[CH:8]=2)[N:3]=1.[C:18]([C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[C:23]([Cl:30])[CH:22]=1)([OH:20])=[O:19].C([O-])([O-])=O.[K+].[K+].Cl>COCCOCCO.O.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:30][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][C:24]=1[C:2]1[C:11]([C:12]([F:15])([F:14])[F:13])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:16][CH3:17])[CH:8]=2)[N:3]=1)[C:18]([OH:20])=[O:19]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 17750227SimtuzumabHCID 53212388HCID 53212388, compound2×

Product 1

HCID 67974881HCID 67974881, compoundYield 68.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 8134Diethylene Glycol Monomethyl EtherSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-chloro-6-methoxy-3-(trifluoromethyl)quinoxaline (Intermediate 11, 150 mg, 0.571 mmol), 4-carboxy-2-chlorophenylboronic acid (115 mg, 0.571 mmol), K2CO3 (160 mg, 1.14 mmol) and Pd(dppf)Cl2 (50 mg, 0.0612 mmol) in diethylene glycol monomethyl ether (2 mL) and water (0.6 mL) was stirred at 120° C. under N2 atmosphere for 2 hours. The resulting mixture was cooled to room temperature and diluted with water (50 mL), acidified with aqueous HCl (2M) until pH=5, extracted with EtOAc (50 mL×3), dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (PE/EtOAc=1/1) to give the product (150 mg, yield 68%) as a solid.

Workup

  1. temperatureThe resulting mixture was cooled to room temperature
  2. extractionextracted with EtOAc (50 mL×3)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography on silica gel (PE/EtOAc=1/1)

Sources & evidence

ORD record
ord-936fc3de6bcf4ddcaaf276316438219e
Source dataset
uspto-grants-2016_06
Patent number
US09364481B2

Reaction notes

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