2-Bromopyridine → HCID 67376913, compound

HRID 875037Notes

Reaction equation

HRID 875037 reaction equation
[C:1]([N:8]1[CH2:13][C@@H:12]2[CH2:14][C@H:9]1[CH2:10][NH:11]2)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Br[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.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].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[N:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[N:11]1[CH2:10][C@@H:9]2[CH2:14][C@H:12]1[CH2:13][N:8]2[C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

8

Reactant 3

HCID 79732-BromopyridineHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 23676156Sodium t-butoxide

Product 1

HCID 67376913HCID 67376913, compoundYield 49%

Reagents, catalysts & solvents 4

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of BINAP (31 mg, 0.05 mmol) and Pd2dba3 (230 mg, 0.03 mmol) were taken in toluene and the solution was heated to 85° C. for 10 min under argon atmosphere. The solution was cooled to 40° C. and (1S,4S)-2-boc-2,5-diazabicyclo[2.2.1]heptane (250 mg, 1.26 mmol) was added, followed by 2-bromo pyridine (218 mg, 1.38 mmol) and sodium tert-butoxide (194 mg, 2.0 mmol). The reaction mixture was heated to 85° C. for 5 h, cooled to room temperature, diluted with EtOAc and filtered through Celite. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluent 20-30% EtOAc in petroleum ether) to get (1S,4S)-tert-butyl 5-(pyridin-2-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (170 mg, yield 49%). 1H NMR (300 MHz, CDCl3) δ 8.14 (d, J=4.6 Hz, 1H), 7.47-7.42 (t, J=7.7 Hz, 1H), 6.59-6.55 (m, 1H), 6.35-6.32 (d, J=8.6 Hz, 1H), 4.90-4.79 (m, 1H), 4.67-4.52 (m, 1H), 3.57-3.35 (m, 4H), 1.96-1.92 (m, 2H), 1.46-1.42 (m, 9H). MS (ESI) m/z: Calculated for C15H21N3O2: 275.16. found: 276.1 (M+H)+

Workup

  1. temperatureThe solution was cooled to 40° C.
  2. temperatureThe reaction mixture was heated to 85° C. for 5 h
  3. temperaturecooled to room temperature
  4. filtrationfiltered through Celite
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluent 20-30% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-5bd1ed1b61894dc5aeb158612b8af74f
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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