1,3-Propanediol → HCID 69413856, compound

HRID 1593956Notes

Reaction equation

HRID 1593956 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([N:9]2[CH2:14][C@@H:13]3[CH2:15][C@H:10]2[CH2:11][N:12]3[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[N:6][C:7]=1Cl.[S:23]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24]1.C(=O)([O-])[O-].[K+].[K+].C(O)CCO.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[OH-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[S:23]1[CH:27]=[CH:26][C:25]([C:2]2[N:3]=[CH:4][C:5]([N:9]3[CH2:14][C@@H:13]4[CH2:15][C@H:10]3[CH2:11][N:12]4[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[N:6][CH:7]=2)=[CH:24]1

Participants

9

Reactant 6

HCID 104421,3-PropanediolHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 581760Thiophene-3-boronic acidHCID 86598716HCID 86598716, compound

Product 1

HCID 69413856HCID 69413856, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-[5-bromo-6-chloro-2-pyrazinyl]-(1S,4S)-5-tert-butoxycarbonyl-2,5-diazabicyclo-[2.2.1]-heptane (4.0 g, 10.3 mmol), 3-thiophene boronic acid, aqueous potassium carbonate (15.4 ml, 2 M), 1,3-propandiol (2.34 g, 30.8 mmol), palladacycle (96 mg, 0.10 mmol), tri-tert-butylphosphine (83 mg, 0.41 mmol), palladium acetate (46 mg, 0.20 mmol) and dioxane (40 ml) was stirred at reflux for 5 days. Aqueous sodium hydroxide (50 ml, 1 M) was added and the mixture was extracted with ethyl acetate (2×30 ml). Chromatography on silica gel with ethyl acetate and petroleum (1:1) gave the title compound as an oil. Yield 1.46 g (41%). This single step also includes 6-dechlorination.

Workup

  1. temperatureat reflux for 5 days
  2. extractionthe mixture was extracted with ethyl acetate (2×30 ml)

Sources & evidence

ORD record
ord-cf73bd5b016942ac8ce28c0d7e298615
Source dataset
uspto-grants-2007_11
Patent number
US07300933B2

Reaction notes

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