Sodium Carbonate → HCID 59272478, compound

HRID 558154Notes

Reaction equation

HRID 558154 reaction equation
[N:1]1([CH2:6][CH2:7][NH:8][C:9]2[N:14]=[C:13]([C:15]3[S:19][C:18]4[C:20](B5OC(C)(C)C(C)(C)O5)=[CH:21][CH:22]=[CH:23][C:17]=4[CH:16]=3)[C:12]([F:33])=[CH:11][N:10]=2)[CH:5]=[CH:4][N:3]=[N:2]1.Br[C:35]1[CH:36]=[C:37]([F:44])[CH:38]=[C:39]2[C:43]=1[NH:42][CH:41]=[CH:40]2.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-].C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+].[F-].[Cs+]>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.CS(C)=O.O1CCOCC1.CN(C=O)C>[N:1]1([CH2:6][CH2:7][NH:8][C:9]2[N:14]=[C:13]([C:15]3[S:19][C:18]4[C:20]([C:35]5[CH:36]=[C:37]([F:44])[CH:38]=[C:39]6[C:43]=5[NH:42][CH:41]=[CH:40]6)=[CH:21][CH:22]=[CH:23][C:17]=4[CH:16]=3)[C:12]([F:33])=[CH:11][N:10]=2)[CH:5]=[CH:4][N:3]=[N:2]1

Participants

12

Reactant 6

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 25953Cesium fluorideHCID 38528797-bromo-5-fluoro-1H-indoleHCID 17749109Barium hydroxide, octahydrateHCID 66738069HCID 66738069, compound

Product 1

HCID 59272478HCID 59272478, compoundYield 43.1%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Combine N-(2-(1H-1,2,3-triazol-1-yl)ethyl)-5-fluoro-4-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)pyrimidin-2-amine (0.12 g, 0.26 mmol), 7-bromo-5-fluoro-1H-indole (64 mg, 0.28 mmol, synthesized based on reference: Manfred S.; Assunta G.: Frédéric L., Eur. J. Org. Chem. 2006, 2956-2069), barium hydroxide octahydrate (0.24 g, 0.77 mmol, alternatively sodium carbonate, potassium carbonate, cesium fluoride), Pd(dppf)Cl2 (20 mg, 0.03 mmol) in 2 mL of mixed solvent of DMF (alternatively dioxane, DMSO) and water (4/1, v/v). Purge the mixture with N2 three times. Heat the reaction mixture to 80° C. for 4 h (HPLC monitor) (or microwave reactor). Cool to RT. Dilute with chloroform/IPA (3:1, v/v) 50 mL. Wash with water, aqueous saturated sodium chloride and dry over magnesium sulfate. Remove the organic solvent to give the crude product. Purify the residue by column chromatography (hexane to ethyl acetate, or methylene chloride and methanol) to give the title compound (0.053 g, 43%). MS (ES) m/z 474 [M+1]+.

Workup

  1. customPurge the mixture with N2 three times
  2. temperatureCool to RT
  3. additionDilute with chloroform/IPA (3:1
  4. washWash with water, aqueous saturated sodium chloride
  5. dry with materialdry over magnesium sulfate
  6. customRemove the organic solvent
  7. customto give the crude product
  8. customPurify the residue by column chromatography (hexane to ethyl acetate, or methylene chloride and methanol)

Sources & evidence

ORD record
ord-e17a4f135a9e4fbcb4abdc1921746228
Source dataset
uspto-grants-2011_11
Patent number
US08063035B2

Reaction notes

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