1,2-Dichloroethane → 6-(2-(3-((3,4-dichlorophenyl)amino)-1,2,4-oxadiazol-5-yl)ethyl)-1-(4-methoxybenzyl)-3,4-dihydroquinolin-2(1H)-one

HRID 1023172Notes

Reaction equation

HRID 1023172 reaction equation
[CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][N:8]2[C:17]3[C:12](=[CH:13][C:14]([CH2:18][CH2:19][C:20](O)=[O:21])=[CH:15][CH:16]=3)[CH2:11][CH2:10][C:9]2=[O:23])=[CH:5][CH:4]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.[Cl:49][C:50]1[CH:51]=[C:52]([NH:57]/[C:58](/[NH2:61])=[N:59]/O)[CH:53]=[CH:54][C:55]=1[Cl:56].S([O-])([O-])(=O)=O.[Na+].[Na+]>CN(C=O)C>[Cl:49][C:50]1[CH:51]=[C:52]([NH:57][C:58]2[N:61]=[C:20]([CH2:19][CH2:18][C:14]3[CH:13]=[C:12]4[C:17](=[CH:16][CH:15]=3)[N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:25][CH:24]=3)[C:9](=[O:23])[CH2:10][CH2:11]4)[O:21][N:59]=2)[CH:53]=[CH:54][C:55]=1[Cl:56]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 24436Sodium SulfateHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 866804133-(1-(4-Methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)propanoic acidHCID 178513435HCID 178513435, compound

Product 1

HCID 866804156-(2-(3-((3,4-dichlorophenyl)amino)-1,2,4-oxadiazol-5-yl)ethyl)-1-(4-methoxybenzyl)-3,4-dihydroquinolin-2(1H)-oneYield 19.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 3-(1-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)propanoic acid (200 mg, 0.589 mmol) in DMF (3 mL) were added HOBT (99 mg, 0.648 mmol), EDC (124 mg, 0.648 mmol), and DIPEA (0.154 mL, 0.884 mmol). The reaction mixture was stirred for 30 minutes, then (E)-1-(3,4-dichlorophenyl)-2-hydroxyguanidine (130 mg, 0.589 mmol) was added followed by sodium sulfate (419 mg, 2.95 mmol). The reaction mixture was heated at 110° C. for 12 h, then concentrated, diluted with water, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel using 10-100% EtOAc/hexane to give 6-(2-(3-((3,4-dichlorophenyl)amino)-1,2,4-oxadiazol-5-yl)ethyl)-1-(4-methoxybenzyl)-3,4-dihydroquinolin-2(1H)-one as a yellow solid (0.06 g, 11% yield). 1H NMR 400 MHz, DMSO-d6: δ 2.65-2.68 (m, 2H), 2.90 (t, J=15.20 Hz, 2H), 2.95 (t, J=12.40 Hz, 2H), 3.16 (t, J=15.20 Hz, 2H), 3.70 (s, 3H), 5.05 (s, 2H), 6.84-6.90 (m, 3H), 7.02-7.04 (m, 1H), 7.14-7.16 (m, 3H), 7.38-7.41 (m, 1H), 7.57 (d, J=8.80 Hz, 1H), 7.69 (s, 1H), 10.23 (s, 1H). LCMS (ES-API), RT: 2.20 min; m/z 523.0 [M−H]−.

Workup

  1. concentrationconcentrated
  2. additiondiluted with water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography on silica gel using 10-100% EtOAc/hexane

Sources & evidence

ORD record
ord-8297713146b74fbdbf04c8425fe4d4d0
Source dataset
uspto-grants-2014_05
Patent number
US08722670B2

Reaction notes

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