Sodium Carbonate → methyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1-(triisopropylsilyl)-1H-indol-6-yl)picolinate

HRID 923696Notes

Reaction equation

HRID 923696 reaction equation
[F:1][C:2]1[C:3](B2OC(C)(C)C(C)(C)O2)=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:8]=[CH:7]2.[NH2:30][C:31]1[C:36]([F:37])=[C:35](Cl)[N:34]=[C:33]([C:39]([O:41][CH3:42])=[O:40])[C:32]=1[Cl:43].C(=O)([O-])[O-].[Na+].[Na+].C(#N)C.O>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.C(OCC)(=O)C>[NH2:30][C:31]1[C:36]([F:37])=[C:35]([C:3]2[C:2]([F:1])=[C:10]3[C:6]([CH:7]=[CH:8][N:9]3[Si:11]([CH:15]([CH3:17])[CH3:16])([CH:12]([CH3:13])[CH3:14])[CH:18]([CH3:20])[CH3:19])=[CH:5][CH:4]=2)[N:34]=[C:33]([C:39]([O:41][CH3:42])=[O:40])[C:32]=1[Cl:43]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 18373917Acetonitrile--water (1/1)HCID 22677265Methyl 4-amino-3,6-dichloro-5-fluoropicolinateHCID 904186597-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-indole

Product 1

HCID 90418343methyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1-(triisopropylsilyl)-1H-indol-6-yl)picolinateYield 43.9%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

7-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-indole (1.0 g, 2.4 mmol), methyl 4-amino-3,6-dichloro-5-fluoropicolinate (630 mg, 2.6 mmol), sodium carbonate (250 mg, 2.4 mmol) and with bis(triphenylphosphine)palladium(II) chloride (170 mg, 0.24 mmol) were combined in 10 mL of 1:1 v/v acetonitrile-water and heated at 110° C. for 30 min in a Biotage Initiator microwave reactor. The mixture was stirred with 30 mL ethyl acetate and 20 mL water and filtered through glass wool to remove dark solids. The organic phase was washed with sat. NaCl, dried (Na2SO4), and evaporated. Purification by flash chromatography (SiO2; eluting with 0-30% ethyl acetate in hexanes) provided 520 mg of the title compound as a white solid (520 mg; 42).

Workup

  1. filtrationfiltered through glass wool
  2. customto remove dark solids
  3. washThe organic phase was washed with sat. NaCl
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customPurification
  7. washby flash chromatography (SiO2; eluting with 0-30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c8bf0b0b22444e5ebecd53d967c5a101
Source dataset
uspto-grants-2016_03
Patent number
US09278985B2

Reaction notes

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