Dicyclohexylcarbodiimide → 1-(4-(3-(3-Chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)phenyl)cyclopropanecarbonitrile

HRID 1172972Notes

Reaction equation

HRID 1172972 reaction equation
[C:1]([C:3]1([C:6]2[CH:14]=[CH:13][C:9]([C:10]([OH:12])=O)=[CH:8][CH:7]=2)[CH2:5][CH2:4]1)#[N:2].[Cl:15][C:16]1[CH:17]=[C:18]([CH:23]=[CH:24][C:25]=1[O:26][CH:27]([CH3:29])[CH3:28])/[C:19](=[N:21]/O)/[NH2:20].C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(#N)C>[Cl:15][C:16]1[CH:17]=[C:18]([C:19]2[N:21]=[C:10]([C:9]3[CH:8]=[CH:7][C:6]([C:3]4([C:1]#[N:2])[CH2:4][CH2:5]4)=[CH:14][CH:13]=3)[O:12][N:20]=2)[CH:23]=[CH:24][C:25]=1[O:26][CH:27]([CH3:29])[CH3:28]

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 595565653-chloro-N'-hydroxy-4-propan-2-yloxybenzenecarboximidamideHCID 595567074-(1-Cyanocyclopropyl)benzoic acid

Product 1

HCID 595566001-(4-(3-(3-Chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)phenyl)cyclopropanecarbonitrileYield 23.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
160 °C

Procedure

A 20 mL microwave vial was charged with 4-(1-cyanocyclopropyl)benzoic acid (720 mg, 3.85 mmol), (Z)-3-chloro-N′-hydroxy-4-isopropoxybenzimidamide (880 mg, 3.85 mmol), DCC (873 mg, 4.23 mmol), HOBT (648 mg, 4.23 mmol), ACN (10 ml), and DIEA (1.478 ml, 8.46 mmol). The vial was capped and heated to 160° C. via microwave irradiation for 25 minutes (max 300 W). Solvent was removed under reduced pressure and crude oil was purified by flash column chromatography (Analogix system, heptane/ethyl acetate, 0-45% ethyl acetate over 30 min; 80 g column, 60 mL/min flow rate). Fractions containing product were combined, rotovapped, and dried in a vacuum oven overnight to give 1-(4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)phenyl)cyclopropanecarbonitrile (347 mg, 23.8%) as a yellow solid. LCMS (Table 1, Method c) Rt=3.19 min, m/z 380.43 (M+H)+; 1H NMR (400 MHz, DMSO)) δ ppm 8.22-8.12 (m, 2H), 8.05 (d, 1H), 7.99 (dd, 2.14 Hz, 1H), 7.62-7.55 (m, 2H), 7.38 (d, 1H), 4.82 (td, 1H), 1.90 (q, 2H), 1.67 (q, 2H), 1.38-1.33 (m, 6H).

Workup

  1. customThe vial was capped
  2. customSolvent was removed under reduced pressure
  3. customcrude oil was purified by flash column chromatography (Analogix system, heptane/ethyl acetate, 0-45% ethyl acetate over 30 min; 80 g column, 60 mL/min flow rate)
  4. additionFractions containing product
  5. customdried in a vacuum oven overnight

Sources & evidence

ORD record
ord-b9c522cd88d949729e9f2c65155c880e
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

Loading…