2-Fluoropyridine → HCID 67433925, compound

HRID 2036586Notes

Reaction equation

HRID 2036586 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH:12]C(=O)OC(C)(C)C)[CH3:11])[NH:7][C:6]=2[CH:20]=1.F[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].FC1C=CC2N=C(C(N)C)N(C3C=CC=CN=3)C=2C=1>CCOC(C)=O.CN(C)C(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[C:8]([CH:10]([NH2:12])[CH3:11])=[N:7][C:6]=2[CH:20]=1

Participants

7

Reactant 4

HCID 97462-FluoropyridineHCID 10796Cesium carbonateHCID 58459264HCID 58459264, compoundHCID 58459397HCID 58459397, compound

Product 1

HCID 67433925HCID 67433925, compoundYield 31.6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

To a microwave vial was added (S)-tert-butyl 1-(6-fluoro-1H-benzo[d]imidazol-2-yl)ethylcarbamate (Prepared in Example 16, 0.5126 g, 1.835 mmol), N,N-Dimethylacetamide (4.08 mL), 2-fluoropyridine (0.189 mL, 2.202 mmol), and cesium carbonate (1.196 g, 3.67 mmol). The mixture was heated for 40 min in the microwave reactor (Temperature: 150° C. Pressure: 92˜94 psi, Power: 8˜10 W). At this time, the mixture was poured into EtOAc (100 mL), filtered and then concentrated on the high vacuum to remove most of the DMA. The residue was purified by silica gel column chromatography on a 40 g of Redi-Sep™ column using 0 to 20% gradient of EtOAc in hexane over 14 min, then 20% EtOAc in hexane for 14 min, then 20 to 50% gradient of EtOAc in hexane over 14 min, and then 50% EtOAc in hexane for 14 min as eluent to give a mixture of four isomer of two regioisomers and two stereoisomer of each regioisomer, 1-(6-fluoro-1-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)ethanamine and 1-(5-fluoro-1-(pyridin-2-yl)-1H-benzo[d]imidazol-2-yl)ethanamine (0.1486 g, 0.580 mmol, 31.6% yield) as a yellow syrup: LC-MS (ESI) m/z 257.0 [M+H]+.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated on the high vacuum
  3. customto remove most of the DMA
  4. customThe residue was purified by silica gel column chromatography on a 40 g of Redi-Sep™ column
  5. customover 14 min
  6. wait20 to 50% gradient of EtOAc in hexane over 14 min
  7. custom50% EtOAc in hexane for 14 min as eluent to give

Sources & evidence

ORD record
ord-fdfa8f58388e47ffa4230cd622dacf0b
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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