Dicyclohexylcarbodiimide → HCID 59556621, compound

HRID 1172965Notes

Reaction equation

HRID 1172965 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])/[C:5](=[N:7]/[OH:8])/[NH2:6].Br[C:17]1[CH:25]=[CH:24][C:20]([C:21](O)=O)=[CH:19][N:18]=1.C1CCC(N=C=NC2CCCCC2)CC1.[CH:41]1[CH:42]=[CH:43][C:44]2[N:49]([OH:50])[N:48]=[N:47][C:45]=2[CH:46]=1.CCN(C(C)C)C(C)C>C(#N)C>[N:49]1([O:50][C:17]2[N:18]=[CH:19][C:20]([C:21]3[O:8][N:7]=[C:5]([C:4]4[CH:9]=[CH:10][C:11]([O:12][CH:13]([CH3:15])[CH3:14])=[C:2]([Cl:1])[CH:3]=4)[N:6]=3)=[CH:24][CH:25]=2)[C:44]2[CH:43]=[CH:42][CH:41]=[CH:46][C:45]=2[N:47]=[N:48]1

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2389326-Bromonicotinic acidHCID 595565653-chloro-N'-hydroxy-4-propan-2-yloxybenzenecarboximidamide

Product 1

HCID 59556621HCID 59556621, compoundYield 65.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 25 mL microwave reaction vial was charged with (Z)-3-chloro-N′-hydroxy-4-isopropoxybenzimidamide (0.1 g, 0.437 mmol), 6-bromonicotinic acid (0.097 g, 0.481 mmol), and DCC (0.099 g, 0.481 mmol) in acetonitrile (2.403 ml). HOBT (0.074 g, 0.481 mmol) was added in one portion, the resulting suspension was allowed to stir at room temperature for 10 min. DIEA (0.168 ml, 0.962 mmol) was added dropwise, the reaction mixture was heated at 120° C. for 30 min under microwave irradiation (Biotage Optimizer, 300 W). The solution was cooled, the reaction mixture was partitioned between EtOAc (50 mL) and water (50 mL), the organic layer was washed by water (2×50 mL), and concentrated afforded yellow solid, which was purified via silica gel chromatography (12 g, 20% EtOAc:Heptane) to afford 5-(6-(1H-benzo[d][1,2,3]triazol-1-yloxy)pyridin-3-yl)-3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazole (0.128 g, 0.285 mmol, 65.2% yield) as a white solid. LC/MS (Table 1, Method a) Rt=3.74 min.; MS m/z: 449.18 (M+H)+. 1H NMR (400 MHz, Solvent d-DMSO) ppm 8.88 (dd, J=2.25, 0.65 Hz, 1H), 8.62 (dd, J=8.68, 2.27 Hz, 1H), 8.15 (t, J=5.28 Hz, 2H), 7.97 (dd, J=8.62, 2.14 Hz, 1H), 7.55 (d, J=0.96 Hz, 1H), 7.52-7.44 (m, 2H), 7.36 (dd, J=8.68, 0.70 Hz, 1H), 7.03 (d, J=8.87 Hz, 1H), 4.73-4.61 (m, 1H), 1.46-1.40 (m, 6H).

Workup

  1. customA 25 mL microwave reaction
  2. temperaturethe reaction mixture was heated at 120° C. for 30 min under microwave irradiation (Biotage Optimizer, 300 W)
  3. temperatureThe solution was cooled
  4. customthe reaction mixture was partitioned between EtOAc (50 mL) and water (50 mL)
  5. washthe organic layer was washed by water (2×50 mL)
  6. concentrationconcentrated
  7. customafforded yellow solid, which
  8. customwas purified via silica gel chromatography (12 g, 20% EtOAc:Heptane)

Sources & evidence

ORD record
ord-60124d81818441f4954fd3645074c212
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

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