Sodium Carbonate → HCID 25120563, compound

HRID 1640927Notes

Reaction equation

HRID 1640927 reaction equation
[F:1][C:2]1[C:3]([C:16]2[S:20][C:19]3[C:21](B4OC(C)(C)C(C)(C)O4)=[CH:22][CH:23]=[CH:24][C:18]=3[CH:17]=2)=[N:4][C:5]([NH:8][CH2:9][CH2:10][N:11]2[CH:15]=[CH:14][N:13]=[N:12]2)=[N:6][CH:7]=1.[F:34][C:35]1C2[C:38](=[N:39][CH:40]=CC=2Br)[NH:37][CH:36]=1.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-].C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+].C(=O)(O)[O-].[Na+].C(Cl)(Cl)Cl.[CH3:77][CH:78](O)[CH3:79]>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.CC#N.CS(C)=O.C1COCC1.O1CCOCC1.CN(C=O)C>[N:11]1([CH2:10][CH2:9][NH:8][C:5]2[N:4]=[C:3]([C:16]3[S:20][C:19]4[C:21]([C:77]5[C:35]([F:34])=[CH:36][N:37]=[C:38]6[NH:39][CH:40]=[CH:79][C:78]=56)=[CH:22][CH:23]=[CH:24][C:18]=4[CH:17]=3)[C:2]([F:1])=[CH:7][N:6]=2)[CH:15]=[CH:14][N:13]=[N:12]1

Participants

15

Reactant 7

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 17749109Barium hydroxide, octahydrateHCID 21906603Chloroform isopropyl alcoholHCID 66738069HCID 66738069, compoundHCID 667381024-Bromo-3-fluoro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 25120563HCID 25120563, compoundYield 47%

Reagents, catalysts & solvents 7

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Combine {5-fluoro-4-[7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophen-2-yl]-pyrimidin-2-yl}-(2-[1,2,3]triazol-1-yl-ethyl)-amine (0.105 g, 0.23 mmol), 3-fluoro-4-bromo-1H-pyrrolo[2,3-b]pyridine (51 mg, 0.30 mmol), barium hydroxide octahydrate (0.21 g, 0.68 mmol, alternatively sodium carbonate, potassium carbonate, sodium bicarbonate), Pd(dppf)Cl2 (20 mg, 0.025 mmol) in 2 mL of mixed solvent of DMF (alternatively dioxane, THF, DMSO, and CH3CN) and water (4/1, v/v). Heat the reaction mixture to 80° C. for 2.5 h. (or microwave heating for 10-60 min). Cool to RT. Dilute it with chloroform/IPA (3:1, v/v) 50 mL. Wash it with water and saturated aqueous sodium chloride and dry over magnesium sulfate. Remove the organic solvent to give the crude product. Purify by column chromatography (hexane to ethyl acetate) to afford the title compound (0.05 g, 47%). MS (ES) m/z 475 [M+1]+.

Workup

  1. temperature(or microwave heating for 10-60 min)
  2. temperatureCool to RT
  3. washWash it with water and saturated aqueous sodium chloride
  4. dry with materialdry over magnesium sulfate
  5. customRemove the organic solvent
  6. customto give the crude product
  7. customPurify by column chromatography (hexane to ethyl acetate)

Sources & evidence

ORD record
ord-c099a162d9de41d3a4ac2d3f8fcebe00
Source dataset
uspto-grants-2012_02
Patent number
US08114872B2

Reaction notes

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