Cesium carbonate → HCID 178461952, compound

HRID 243507Notes

Reaction equation

HRID 243507 reaction equation
Br[C:2]1[C:7]2[N:8]([CH3:23])[C:9]([C@@H:11]([NH:13][C:14]3[N:22]=[CH:21][N:20]=[C:19]4[C:15]=3[N:16]=[CH:17][NH:18]4)[CH3:12])=[N:10][C:6]=2[CH:5]=[CH:4][C:3]=1[F:24].[N:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:24][C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[C:9]([C@@H:11]([NH:13][C:14]3[N:22]=[CH:21][N:20]=[C:19]4[C:15]=3[N:16]=[CH:17][NH:18]4)[CH3:12])[N:8]([CH3:23])[C:7]=2[C:2]=1[C:28]1[CH:29]=[CH:30][N:25]=[CH:26][CH:27]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 178461925N-[(1S)-1-(7-bromo-6-fluoro-1-methyl-benzimidazol-2-yl)ethyl]-9H-purin-6-amine

Product 1

HCID 178461952HCID 178461952, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of [(S)-1-(7-bromo-6-fluoro-1-methyl-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine, (0.10 g, 0.26 mmol), 4-pyridylboronic acid (0.041 g, 0.33 mmol), tetrakis(triphenylphosphine)palladium(0) (0.015 g, 0.01 mmol) and caesium carbonate (0.17 g, 0.51 mmol) in dioxane (3 mL) and water (1.5 mL) was placed in a sealed tube and degassed with nitrogen for 5 minutes, then heated for 45 minutes at 140° C. by microwave irradiation. The resulting mixture was loaded onto an Isolute® SCX-2 cartridge then washed with MeOH and the product eluted with 2M NH3/MeOH and concentrated in vacuo. The residue was purified by chromatography (SiO2, 0-10% (2M ammonia in methanol) in DCM) then by preparative HPLC (Phenomenex Gemini 5 μm C18 on a 78 min gradient 20-98% 0.1% HCO2H in acetonitrile/water) to give 433 as a white solid (0.019 g, 20%). LCMS (Method K): RT 2.10 min [M+H]+ 389.1. 1H NMR (DMSO-d6, 400 MHz): δ 12.70 (1H, s), 8.70 (2H, s), 8.25-8.13 (2H, m), 7.95 (1H, d), 7.71 (1H, dd, J=8.80, 4.80 Hz), 7.53 (2H, d, J=17.59 Hz), 7.17 (1H, dd, J=10.45, 8.79 Hz), 5.85-5.73 (1H, m), 3.30 (3H, s), 1.66 (3H, d, J=6.75 Hz). Signals split due to presence of tautomers

Workup

  1. customwas placed in a sealed tube
  2. customdegassed with nitrogen for 5 minutes
  3. washthen washed with MeOH
  4. washthe product eluted with 2M NH3/MeOH
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography (SiO2, 0-10% (2M ammonia in methanol) in DCM)

Sources & evidence

ORD record
ord-25473372934f40ae9c944160312bb151
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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