1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-(3-Chloromethyl-[1,2,4]oxadiazol-5-yl)-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 2427513Notes

Reaction equation

HRID 2427513 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:24](O)=[O:25])[CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=1)[CH2:7]2.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:48][CH2:49][C:50]([NH:52]O)=[NH:51]>CN(C=O)C.CCOC(C)=O>[Cl:48][CH2:49][C:50]1[N:52]=[C:24]([C:4]2[CH:5]=[C:6]3[C:10](=[C:2]([CH3:1])[CH:3]=2)[C:9](=[O:11])[N:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:21])[F:22])=[CH:15][CH:14]=2)[CH2:7]3)[O:25][N:51]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 53311336HCID 53311336, compoundHCID 178511097HCID 178511097, compound

Product 1

HCID 579495425-(3-Chloromethyl-[1,2,4]oxadiazol-5-yl)-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-oneYield 33%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
135 °C

Procedure

7-Methyl-1-oxo-2-(4-trifluoromethoxybenzyl)-2,3-dihydro-1H-isoindole-5-carboxylic acid (80.0 mg, 0.49 mmol), EDCI (104.0 mg, 0.54 mmol), HOBT (73.0 mg, 0.54 mmol) and 2-chloro-N-hydroxyacetamidine (59.0 mg, 0.54 mmol) were mixed in DMF (4.0 mL) over the weekend. The reaction mixture was diluted with EtOAc and washed with water, brine, dried over sodium sulfate, filtered and concentrated. The product was subjected to column chromatography (100% EtOAc). The product was heated to 135° C. in DMF for 1.5 hours. The reaction mixture was cooled and diluted with ethyl acetate, washed with water, brine, dried over sodium sulfate, filtered and concentrated. The product was purified by column chromatography to yield the title compound as a brown oil (63.0 mg, 33%). 1H NMR (300 MHz, CDCl3): δ 8.01 (d, 2H), 7.37 (d, 2H), 7.21 (d, 2H), 4.81 (s, 2H), 4.69 (s, 2H), 4.34 (s, 2H), 2.85 (s, 3H).

Workup

  1. washwashed with water, brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. temperatureThe reaction mixture was cooled
  6. additiondiluted with ethyl acetate
  7. washwashed with water, brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe product was purified by column chromatography

Sources & evidence

ORD record
ord-1525ad6b9e564b0095dc677aa401cc63
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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