Cesium fluoride → HCID 90418194, compound

HRID 923691Notes

Reaction equation

HRID 923691 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6](B(O)O)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[NH2:13][C:14]1[C:19]([F:20])=[C:18](Cl)[N:17]=[C:16]([C:22]([O:24][CH3:25])=[O:23])[C:15]=1[Cl:26].[F-].[Cs+].P(C1C=C(S([O-])(=O)=O)C=CC=1)(C1C=C(S([O-])(=O)=O)C=CC=1)C1C=C(S([O-])(=O)=O)C=CC=1.[Na+].[Na+].[Na+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[NH2:13][C:14]1[C:19]([F:20])=[C:18]([C:6]2[CH:5]=[C:4]3[C:9](=[CH:8][CH:7]=2)[NH:1][CH:2]=[CH:3]3)[N:17]=[C:16]([C:22]([O:24][CH3:25])=[O:23])[C:15]=1[Cl:26]

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 27343615-Indolylboronic acidHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)HCID 22677265Methyl 4-amino-3,6-dichloro-5-fluoropicolinate

Product 1

HCID 90418194HCID 90418194, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

1H-Indol-5-ylboronic acid (220 mg, 1.4 mmol, 1.1 equiv) and methyl 4-amino-3,6-dichloro-5-fluoropicolinate (300 mg, 1.3 mmol, 1.0 equiv) were sequentially added to a 5 mL Biotage microwave vessel, followed by cesium fluoride (380 mg, 2.5 mmol, 2.0 equiv), palladium(II) acetate (14 mg, 0.063 mmol, 0.05 equiv), and sodium 3,3′,3″-phosphinetriyltribenzenesulfonate (71 mg, 0.13 mmol, 0.10 equiv). A 3:1 mixture of water:acetonitrile (2.5 mL) was added and the resulting dark brown mixture was placed in a Biotage microwave and heated to 150° C. for 5 m, with external IR-sensor temperature monitoring from the side of the vessel. The cooled reaction mixture was diluted with water (50 mL) and extracted with dichloromethane (15×30 mL). The combined organic layers were dried (sodium sulfate), gravity filtered, and concentrated by rotary evaporation. The residue was purified by reverse phase column chromatography (5% acetonitrile to 100% acetonitrile gradient) to yield the title compound as a tan powder (290 mg, 73%).

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with dichloromethane (15×30 mL)
  3. dry with materialThe combined organic layers were dried (sodium sulfate), gravity
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customThe residue was purified by reverse phase column chromatography (5% acetonitrile to 100% acetonitrile gradient)

Sources & evidence

ORD record
ord-4f570aca46ec4a15a4e42c6f2aa93b62
Source dataset
uspto-grants-2016_03
Patent number
US09278985B2

Reaction notes

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