Potassium Carbonate → HCID 49848668, compound

HRID 1714846Notes

Reaction equation

HRID 1714846 reaction equation
Cl[CH2:2][C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:9]=[C:10]3[C:14](=[C:15]([CH3:17])[CH:16]=2)[C:13](=[O:18])[N:12]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=2)[CH2:11]3)[N:4]=1.C([O-])([O-])=O.[K+].[K+].C(OC([N:44]1[CH2:49][C@@H:48]2[CH2:50][C@H:45]1[CH2:46][NH:47]2)=O)(C)(C)C>CC#N.O>[CH:45]12[CH2:50][CH:48]([NH:47][CH2:46]1)[CH2:49][N:44]2[CH2:2][C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:9]=[C:10]3[C:14](=[C:15]([CH3:17])[CH:16]=2)[C:13](=[O:18])[N:12]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=2)[CH2:11]3)[N:4]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 59465461HCID 59465461, compound

Product 1

HCID 49848668HCID 49848668, compoundYield 72.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 5-(5-chloromethyl-[1,2,4]oxadiazol-3-yl)-7-methyl-2-(4-trifluoromethoxybenzyl)-2,3-dihydroisoindol-1-one (100 mg, 0.228 mmol) in MeCN (4 mL) was added K2CO3 (95 mg, 0.684 mmol) and (1s,4s)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (90 mg, 0.451 mmol). After 48 hours the mixture was diluted with water, then extracted with EtOAc. The organic phase was washed with brine, dried (Na2SO4), filtered, and concentrated to a yellow oil. This residue was dissolved in 1:1 TFA/CH2Cl2 (6 mL) for 30 minutes, then the reaction mixture was concentrated and basified with NaHCO3 to pH˜9-10. The product was extracted with CH2Cl2. The organic phase was washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography on silica (2-8% 2M NH3 in MeOH/CH2Cl2) to provide 5-[5-(2,5-diazabicyclo[2.2.1]hept-2-ylmethyl)-[1,2,4]oxadiazol-3-yl]-7-methyl-2-(4-trifluoromethoxybenzyl)-2,3-dihydroisoindol-1-one as a light yellow solid (83 mg). 1H NMR (300 MHz, CDCl3) δ 7.95 (s, 1H), 7.91 (s, 1H), 7.34 (d, 2H), 7.18 (d, 2H), 4.77 (s, 2H), 4.28 (s, 2H), 4.05 (dd, 2H), 3.57 (d, 2H), 3.20 (d, 1H), 3.13 (dd, 1H), 2.88 (dd, 1H), 2.79 (s, 3H), 2.61 (d, 1H), 1.86 (d, 1H), 1.64 (d, 1H).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic phase was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated to a yellow oil
  6. dissolutionThis residue was dissolved in 1:1 TFA/CH2Cl2 (6 mL) for 30 minutes
  7. concentrationthe reaction mixture was concentrated
  8. extractionThe product was extracted with CH2Cl2
  9. washThe organic phase was washed with brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by column chromatography on silica (2-8% 2M NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-a09bcb0f638048889e51c1b995f08aa4
Source dataset
uspto-grants-2010_09
Patent number
US07799792B2

Reaction notes

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