Ethyl Acetate → 6-Isopropyl-8-[4-(2-phenyl-thiazol-4-ylmethyl)-[1,4]diazepan-1-yl]-quinoline

HRID 532855Notes

Reaction equation

HRID 532855 reaction equation
Cl.Cl.[N:3]1([C:10]2[CH:11]=[C:12]([CH:20]([CH3:22])[CH3:21])[CH:13]=[C:14]3[C:19]=2[N:18]=[CH:17][CH:16]=[CH:15]3)[CH2:9][CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.Cl[CH2:24][C:25]1[N:26]=[C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[S:28][CH:29]=1.C([O-])([O-])=O.[Cs+].[Cs+].CCOC(C)=O>CN(C=O)C>[CH:20]([C:12]1[CH:13]=[C:14]2[C:19](=[C:10]([N:3]3[CH2:9][CH2:8][CH2:7][N:6]([CH2:24][C:25]4[N:26]=[C:27]([C:30]5[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=5)[S:28][CH:29]=4)[CH2:5][CH2:4]3)[CH:11]=1)[N:18]=[CH:17][CH:16]=[CH:15]2)([CH3:22])[CH3:21]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 2369694-(Chloromethyl)-2-phenyl-1,3-thiazoleHCID 668909958-[1,4]-Diazepan-1-yl-6-isopropyl-quinoline dihydrochloride

Product 1

HCID 593661696-Isopropyl-8-[4-(2-phenyl-thiazol-4-ylmethyl)-[1,4]diazepan-1-yl]-quinolineYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 8-[1,4]-diazepan-1-yl-6-isopropyl-quinoline dihydrochloride (0.34 g, 1 mmol, 1 equiv), 4-chloromethyl-2-phenyl-thiazole (0.21 g, 1 equiv) and Cs2CO3 (1.63 g, 5 equiv) in 5 mL of DMF was heated to 60° C. for 3 hours and then cooled to room temperature. EtOAc (˜70 mL) was added and the mixture washed with saturated aqueous NaHCO3 (70 mL) and brine (70 mL), dried over magnesium sulfate and concentrated. The residue was purified by silica gel flash column chromatography using 5% to 40% EtOAc in hexanes. Silica gel chromatography was repeated using 5% to 10% MeOH in EtOAc to afford the title compound (0.22 g, 50%) as light tan solid. 1H NMR (400 MHz, d6-CD3OD) δ 8.66 (dd, 1H, J=1.8 and 4 Hz), 8.07 (dd. 1H, J=1.5 and 8.4 Hz), 7.91 (m, 1H), 7.90 (d, 1H, J=2.2 Hz), 7.41 (m, 3H), 7.36 (s, 1H), 7.31 (dd, 1H, J=4.0 and 8.0 Hz), 7.16 (d, 1H, J=1.6 Hz), 7.04 (d, 1H, J=1.6 Hz), 3.90 (s, 2H), 3.71 (m, 2H), 3.59 (t, 2H, J=5.6 Hz), 3.11 (m, 2H), 2.92 (m, 3H), 2.10 (m, 2H), 1.31 (d, 6H, J=7.2 Hz). MS (ES) m/z 443.2 (M+H+).

Workup

  1. temperaturecooled to room temperature
  2. washthe mixture washed with saturated aqueous NaHCO3 (70 mL) and brine (70 mL)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-eae8357d02f24040bd92702aa02a5931
Source dataset
uspto-grants-2014_10
Patent number
US08853202B2

Reaction notes

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