1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 10022903, compound

HRID 1791363Notes

Reaction equation

HRID 1791363 reaction equation
C([C:3]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:4]=1[C:5]([OH:7])=O)#N.C[CH2:15][N:16]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[C:35]([O:39][C:40]([N:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH:43]1[C:48](=[NH:51])[NH:49]O)=[O:41])([CH3:38])([CH3:37])[CH3:36]>C(OCC)(=O)C.CN(C=O)C>[C:35]([O:39][C:40]([N:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH:43]1[C:48]1[N:51]=[C:5]([C:4]2[CH:8]=[C:9]([O:12][CH3:13])[CH:10]=[C:11]([C:15]#[N:16])[CH:3]=2)[O:7][N:49]=1)=[O:41])([CH3:38])([CH3:37])[CH3:36]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27742982-cyano-5-methoxybenzoic acidHCID 178451840HCID 178451840, compound

Product 1

HCID 10022903HCID 10022903, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
135 °C

Procedure

DMF (2.0 mL) was added to a mixture of cyano-5-methoxybenzoic acid (160 mg, 0.90 mmol), EDCI (176 mg, 0.92 mmol), HOBt (124.3 mg, 0.92 mmol) and 2-(N-hydroxycarbamimidoyl)-piperidine-1-carboxylic acid tert-butyl ester (224 mg, 0.92 mmol) at room temperature and stirred overnight. The reaction mixture was diluted with ethyl acetate, washed with water (3 times) and brine, dried anhydrous sodium sulfate, filtered and concentrated. DMF (3 mL) was added to the residue and then heated 135° C. for 2.5 h to effect cyclization to oxadiazole. The reaction mixture was diluted with ethyl acetate, washed with water (3 times) and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by flash chromatography on silica gel, eluted with a mixture of ethyl acetate in hexanes afforded 179 mg (56%) of the title compound as a colorless oil. 1H NMR (CDCl3), δ(ppm): 7.99 (s, 1H), 7.84 (d, 1H), 7.35 (s, 1H), 5.56 (bs, 1H), 4.06 (m, 1H), 3.93 (s, 3H), 3.01 (m, 1H), 2.84 (m, 1H), 1.92 (m, 1H), 1.70 (m, 2H), 1.49 (m, 11H).

Workup

  1. washwashed with water (3 times) and brine, dried anhydrous sodium sulfate
  2. filtrationfiltered
  3. concentrationconcentrated
  4. additionDMF (3 mL) was added to the residue
  5. additionThe reaction mixture was diluted with ethyl acetate
  6. washwashed with water (3 times) and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash chromatography on silica gel
  11. washeluted with a mixture of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c116e83071ab4eae99b80de63e45af7c
Source dataset
uspto-grants-2006_07
Patent number
US07074809B2

Reaction notes

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