N-(4-Bromophenyl)-N'-methylcarbamimidato(3-) → HCID 57147987, compound

HRID 380026Notes

Reaction equation

HRID 380026 reaction equation
[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1.Br[C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]([NH:33][CH3:34])=[O:32])=[CH:26][CH:25]=1>C(O)C.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>[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:24]2[CH:25]=[CH:26][C:27]([NH:30][C:31]([NH:33][CH3:34])=[O:32])=[CH:28][CH:29]=2)=[CH:7][CH:6]=1

Participants

5

Reactant 2

HCID 152311N-(4-Bromophenyl)-N'-methylcarbamimidato(3-)HCID 54413593(1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid

Product 1

HCID 57147987HCID 57147987, compoundYield 24.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

Prepared according to the method described in Example 12b) from (1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid (0.149 g, Example 33), N-(4-bromophenyl)-N′-methyl urea (0.225 g) 2M aqueous sodium carbonate (1.0 ml) and tetrakis(triphenylphosphine)palladium (0) (0.028 g) in ethanol (3 ml). The reaction mixture was heated in a sealed vial at 100° C. for 2 hours. After cooling, the solution was concentrated under reduced pressure. The residue was purified by chromatography over silica eluting with tetrahydrofuran:hexane (1:1). The residue was further purified by chromatography over silica gel eluting dichloromethane:ethanol (9:1). The residue was then further purified by reverse-phase HPLC eluting a gradient of 25-100% acetonitrile in 0.1 w/v aqueous ammonium acetate solution. The HPLC fractions were concentrated under reduced pressure, the residue dissolved in ethanol, filtered and concentrated under reduced pressure to give the title compound as a solid (0.050 g).

Workup

  1. customPrepared
  2. temperatureAfter cooling
  3. concentrationthe solution was concentrated under reduced pressure
  4. customThe residue was purified by chromatography over silica eluting with tetrahydrofuran:hexane (1:1)
  5. customThe residue was further purified by chromatography over silica gel
  6. washeluting dichloromethane:ethanol (9:1)
  7. customThe residue was then further purified by reverse-phase HPLC
  8. washeluting a gradient of 25-100% acetonitrile in 0.1 w/v aqueous ammonium acetate solution
  9. concentrationThe HPLC fractions were concentrated under reduced pressure
  10. dissolutionthe residue dissolved in ethanol
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-90b0a5e52a074afb9c57f5079dd48189
Source dataset
uspto-grants-2001_10
Patent number
US06300352B1

Reaction notes

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