Potassium Fluoride → HCID 58266784, compound

HRID 1505978Notes

Reaction equation

HRID 1505978 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]3[C:20]4[CH:26]=[C:25](Br)[CH:24]=[N:23][C:21]=4[NH:22][C:18]=3[CH:17]=[N:16][C:15]=2[C:28]#[N:29])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1.[F-].[K+]>C(#N)C.O.C(=O)([O-])[O-].[Na+].[Na+].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]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]3[C:20]4[CH:26]=[C:25]([C:34]5[CH:33]=[N:32][N:31]([CH3:30])[CH:35]=5)[CH:24]=[N:23][C:21]=4[NH:22][C:18]=3[CH:17]=[N:16][C:15]=2[C:28]#[N:29])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 522689Potassium FluorideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86653496HCID 86653496, compound

Product 1

HCID 58266784HCID 58266784, compoundYield 30.5%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
130 °C

Procedure

A degassed mixture of 3-(3-bromo-6-cyano-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-5-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (160 mg, 0.20 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (54 mg, 0.26 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (20 mg, 0.026 mmol) in 1N aqueous potassium fluoride (0.60 mL, 0.60 mmol) and acetonitrile (0.60 mL) was heated at 130° C. under microwave irradiation for 30 minutes. The reaction mixture was allowed to cool to ambient temperature diluted with water (5 mL) and saturated aqueous sodium carbonate (5 mL) then extracted with ethyl acetate (3×10 mL). The combined organic phase was dried over magnesium sulfate and concentrated in vacuo. The resultant was purified by flash chromatography (silica, 2 g column, Si-SPE cartridge, 0-100% ethyl acetate in DCM then methanol) and trituration with acetonitrile to afford the title compound as a white solid (28 mg, 30%). 1H NMR (CDCl3, 400 MHz): 8.78-8.71 (m, 2H), 8.46 (s, 1H), 7.90 (s, 1H), 7.85-7.80 (m, 1H), 5.81 (s, 0.5H), 5.73 (s, 0.5H), 4.01 (s, 3H), 3.86-3.57 (m, 3H), 2.58-2.40 (m, 1H), 2.37-2.17 (m, 2H), 1.39 (s, 4H), 1.33 (s, 5H). LCMS (Method B): RT=3.09 min, M+H+=460.

Workup

  1. temperatureto cool to ambient temperature
  2. extractionthen extracted with ethyl acetate (3×10 mL)
  3. dry with materialThe combined organic phase was dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resultant was purified by flash chromatography (silica, 2 g column, Si-SPE cartridge, 0-100% ethyl acetate in DCM

Sources & evidence

ORD record
ord-9c745a8ba7974677b77177874f4c6ef6
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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