Triethylamine → 3-[4-(1(S)-phenyl-ethyl-carbamoyl)-phenyl]-5,7-dichloro-3-methyl-1H-quinoline-2,4-dione

HRID 735253Notes

Reaction equation

HRID 735253 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([Cl:12])[CH:9]=[C:8]2[C:3]=1[C:4](=[O:22])[C:5]([C:15]1[CH:20]=[CH:19][C:18](O)=[CH:17][CH:16]=1)([CH3:14])[C:6](=[O:13])[NH:7]2.C(N(CC)CC)C.[CH3:30][C@H:31]([N:38]=[C:39]=[O:40])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>ClCCl>[C:32]1([C@@H:31]([NH:38][C:39]([C:18]2[CH:19]=[CH:20][C:15]([C:5]3([CH3:14])[C:4](=[O:22])[C:3]4[C:8](=[CH:9][C:10]([Cl:12])=[CH:11][C:2]=4[Cl:1])[NH:7][C:6]3=[O:13])=[CH:16][CH:17]=2)=[O:40])[CH3:30])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2724173(S)-(-)-1-Phenylethyl isocyanateHCID 115952095,7-dichloro-3-(4-hydroxy-phenyl)-3-methyl-1H-quinoline-2,4-dione

Product 1

HCID 688189983-[4-(1(S)-phenyl-ethyl-carbamoyl)-phenyl]-5,7-dichloro-3-methyl-1H-quinoline-2,4-dioneYield 82.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5,7-dichloro-3-(4-hydroxy-phenyl)-3-methyl-1H-quinoline-2,4-dione (0.45 g, 1.30 mmol) and triethylamine (0.18 mL) in dichloromethane (15 mL ) was added (S)-methyl benzylisocyanate (0.15 g, 1.56 mmol) at 0° C. The reaction mixture was stirred for 20 hours at room temperature, and then poured into ice water (100 mL). The reaction mixture was extracted with dichloromethane (100 mL×3), washed with brine (100 mL×2), dried over anhydrous MgSO4 and concentrated in vacuo. The residue was purified by a flash column chromatography (n-hexane:EtOAc=7:1) to afford the unseparable diastereomeric 1:1 mixture (0.50 g, 80%) of the objective diastereomers: 1H NMR (500 MHz, DMSO-d6) δ 1.37 (d, J=7.0 Hz, 3H, CH3), 1.54 (s, 3H, CH3, one diastereomeric peaks), 1.64 (s, 3H, CH3, the other diastereomeric peaks), 4.65 (q, 1H, CH), 7.01-7.3 (m, 11H, ArH), 8.35 (br s, 1H, NH), 11.28 (br s, 1H, NH); m.p. 110-115° C. (diastereomeric 1:1 mixture); MS(EI) m/e 483 [M+−1], 335, 269, 120.

Workup

  1. extractionThe reaction mixture was extracted with dichloromethane (100 mL×3)
  2. washwashed with brine (100 mL×2)
  3. dry with materialdried over anhydrous MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by a flash column chromatography (n-hexane:EtOAc=7:1)

Sources & evidence

ORD record
ord-ed1f736da80140d3931345b8e96d378a
Source dataset
uspto-grants-2009_09
Patent number
US07592457B2

Reaction notes

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