Binap, (A+-)- → HCID 15462085, compound

HRID 914734Notes

Reaction equation

HRID 914734 reaction equation
[C@H:1]12[CH2:7][C@H:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[Cl:15][C:16]1[CH:21]=[CH:20][C:19](I)=[CH:18][N:17]=1.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.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)C>[Cl:15][C:16]1[N:17]=[CH:18][C:19]([N:5]2[CH2:6][C@@H:1]3[CH2:7][C@H:4]2[CH2:3][N:2]3[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 43971762-Chloro-5-iodopyridineHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 23676156Sodium t-butoxide

Product 1

HCID 15462085HCID 15462085, compoundYield 60.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
70 °C

Procedure

In a dry, nitrogen-purged flask, tert-butyl (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (330 mg, 1.6 mmol), prepared as described in (J. Med. Chem., (1988) 31, 1598-1611), in anhydrous toluene (6 mL) was treated with 2-chloro-5-iodopyridine (383 mg, 1.6 mmol), available as described in (Tetrahedron Lett., (1993), 34, 7493-7496), Pd2(dba)3 (156 mg, 0.16 mmol), BINAP (212 mg, 0.34 mmol), and sodium tert-butoxide (230 mg, 2.4 mmol). The mixture was heated at 70° C. for 24 hours. The reaction mixture was poured into diethyl ether (10 mL) and washed successively with 1N HCl, saturated NaHCO3, and brine. The organic phase was dried (MgSO4) and concentrated under reduced pressure. The residue was purified on SiO2, eluting with ethyl acetate:hexanes (1:1) to provide the title compound (300 mg, 58% yield) as a light brown solid. 1H NMR (CDCl3, 300 MHz) δ 1.41(s, 4.5H), 1.46(s, 4.5H), 1.93-2.05(m, 2H), 3.14 (d, J=14.7 Hz, 0.5H), 3.35(d, J=14.7 Hz, 0.5H), 3.42(m, 2H), 3.57 (d, 8.45 Hz, 1H), 4.37(s, 1H), 4.53(s, 0.5H), 4.65(s, 0.5H), 6.82(dd, J=2.94, 8.83Hz, 1H), 7.13(d, J=8.46 Hz, 1H), 7.71(s, 1H); MS (DCI/NH3) m/z 310 (M+H)+.

Workup

  1. customIn a dry, nitrogen-purged flask
  2. washwashed successively with 1N HCl, saturated NaHCO3, and brine
  3. dry with materialThe organic phase was dried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified on SiO2
  6. washeluting with ethyl acetate:hexanes (1:1)

Sources & evidence

ORD record
ord-5f31b5f88534407aad75ae4325c72a2f
Source dataset
uspto-grants-2007_09
Patent number
US07265115B2

Reaction notes

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