1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-(5-Chloro-2-fluoro-phenyl)-3-chloromethyl-[1,2,4]oxadiazole

HRID 2102307Notes

Reaction equation

HRID 2102307 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:33][CH2:34][C:35]([NH:37]O)=[NH:36].C1C2C(C3ON=C(N)N=3)CN(C2)C1>CN(C=O)C>[Cl:11][C:8]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([C:4]2[O:6][N:37]=[C:35]([CH2:34][Cl:33])[N:36]=2)[CH:7]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1639383-(3-Amino-1,2,4-oxadiazol-5-yl)-1-azabicyclo(2.2.1)heptaneHCID 27365375-Chloro-2-fluorobenzoic acidHCID 178511097HCID 178511097, compound

Product 1

HCID 431202105-(5-Chloro-2-fluoro-phenyl)-3-chloromethyl-[1,2,4]oxadiazoleYield 56.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

The acyclic intermediate was prepared from 2-fluoro-5-chlorobenzoic acid (550 mg, 3.15 mmol), EDCI (665 mg, 3.47 mmol), HOBT (469 mg, 3.47 mmol) and 2-chloro-N-hydroxy-acetamidine (377 mg, 3.47 mmol) in DMF (10 mL). To effect cyclization to oxadiazole, DMF (15 mL) was added to the intermediate residue and the mixture was heated for 1 hour. The product was purified by flash column chromatography using 10% ethyl acetate in hexane afforded the title compound (438 mg, 56% yield over 2 steps, white solid). 1H NMR (CDCl3) δ (ppm): 8.16 (m, 1H), 7.58 (m, 1H), 7.29 (m, 1H), 4.72 (s, 3H).

Workup

  1. temperaturethe mixture was heated for 1 hour
  2. customThe product was purified by flash column chromatography

Sources & evidence

ORD record
ord-f8fde40d5612458781e87e66d6018327
Source dataset
uspto-grants-2009_08
Patent number
US07576077B2

Reaction notes

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