Potassium Carbonate → 2-[(4-Chlorophenyl)methyl]-5-[3-(2,5-diazabicyclo[2.2.1]hept-2-ylmethyl)-1,2,4-oxadiazol-5-yl]-2,3-dihydro-7-methyl-1H-isoindol-1-one

HRID 388317Notes

Reaction equation

HRID 388317 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][N:7]2[CH2:15][C:14]3[C:9](=[C:10]([CH3:23])[CH:11]=[C:12]([C:16]4[O:20][N:19]=[C:18]([CH2:21]Cl)[N:17]=4)[CH:13]=3)[C:8]2=[O:24])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].C(OC([N:40]1[CH2:45][C@@H:44]2[CH2:46][C@H:41]1[CH2:42][NH:43]2)=O)(C)(C)C>CC#N.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH2:15][C:14]3[C:9](=[C:10]([CH3:23])[CH:11]=[C:12]([C:16]4[O:20][N:19]=[C:18]([CH2:21][N:40]5[CH2:45][CH:44]6[CH2:46][CH:41]5[CH2:42][NH:43]6)[N:17]=4)[CH:13]=3)[C:8]2=[O:24])=[CH:25][CH:26]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 59543992HCID 59543992, compound

Product 1

HCID 251252182-[(4-Chlorophenyl)methyl]-5-[3-(2,5-diazabicyclo[2.2.1]hept-2-ylmethyl)-1,2,4-oxadiazol-5-yl]-2,3-dihydro-7-methyl-1H-isoindol-1-oneYield 58.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(4-chloro-benzyl)-5-(3-chloromethyl-[1,2,4]oxadiazol-5-yl)-7-methyl-2,3-dihydroisoindol-1-one (40 mg, 0.103 mmol) in MeCN (4 mL) was added K2CO3 (0.309 mmol) and (1s,4s)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (31 mg, 0.154 mmol). The mixture was heated at 60° C. overnight. The reaction was cooled and diluted with water, then extracted with EtOAc. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated. Column chromatography on silica (1% 2M NH3 in MeOH/CH2Cl2) provided 2-(4-chlorobenzyl)-5-[3-(2,5-diazabicyclo[2.2.1]hept-2-ylmethyl)-[1,2,4]oxadiazol-5-yl]-7-methyl-2,3-dihydroisoindol-1-one as a brown solid (27 mg). 1H NMR (300 MHz, CDCl3) δ 8.04 (s, 1H), 7.99 (s, 1H), 7.37 (d, 2H), 7.26 (d, 2H), 4.77 (s, 2H), 4.30 (s, 2H), 3.94 (dd, 2H), 3.58 (d, 2H), 3.26 (d, 1H), 3.11 (d, 1H), 2.89 (d, 1H), 2.84 (s, 3H), 2.63 (d, 1H), 1.88 (d, 1H), 1.66 (d, 1H).

Workup

  1. temperatureThe reaction was cooled
  2. extractionextracted with EtOAc
  3. washThe organic phase was washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-0abce50feb314f428550987234ee585b
Source dataset
uspto-grants-2013_02
Patent number
US08377940B2

Reaction notes

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