Cesium carbonate → HCID 118251036, compound

HRID 2283458Notes

Reaction equation

HRID 2283458 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:22]1[C:23]([O:29][CH3:30])=[N:24][CH:25]=[C:26]([Br:28])[CH:27]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:28][C:26]1[CH:27]=[C:22]([NH:1][C@@H:2]2[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]2)[C:23]([O:29][CH3:30])=[N:24][CH:25]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 135677523,5-Dibromo-2-methoxypyridine

Product 1

HCID 118251036HCID 118251036, compoundYield 34.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

(R)-tert-Butyl 3-aminopiperidine-1-carboxylate (2.99 g, 15.0 mmol) and cesium carbonate (9.84 g, 30.0 mmol) were added to a solution of 3,5-dibromo-2-methoxypyridine (4.00 g, 15.0 mmol) in dioxane (100 mL). The mixture was degassed for 20 min and then Xphos (0.692 g, 1.20 mmol) and Pd2(dba)3 (1.10 g, 1.20 mmol) were added. The mixture was stirred at 110° C. for 12 h. The mixture was allowed to cool to room temperature and was filtered through celite and concentrated. The residue was purified by chromatography using 5-10% ethyl acetate in pet ether to give 2 g of the desired compound: 1H NMR (300 MHz, DMSO-d6) 7.44 (narrow m, 1H), 6.95 (s, 1H), 5.15-5.20 (m, 1H), 3.91 (s, 3H), 3.50-3.95 (m, 2H), 3.20-3.40 (m, 1H), 2.80-3.05 (m, 2H), 1.80-1.95 (m, 1H), 1.10-1.70 (m, 3H), 1.36 (s, 9H); MS (ES) m/z 386, 384 (M+).

Workup

  1. customThe mixture was degassed for 20 min
  2. temperatureto cool to room temperature
  3. filtrationwas filtered through celite
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-851046c044ba44a08242f23a2826d8f2
Source dataset
uspto-grants-2015_09
Patent number
US09145393B2

Reaction notes

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