Thionyl Chloride → 3-[6-(4-ethylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]-N-isoxazol-3-yl-4-methylbenzamide

HRID 641952Notes

Reaction equation

HRID 641952 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[N:11]1[C:20](=[O:21])[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([N:22]3[CH2:27][CH2:26][N:25]([CH2:28][CH3:29])[CH2:24][CH2:23]3)[CH:18]=2)[N:13]=[CH:12]1.S(Cl)(Cl)=O.[NH2:34][C:35]1[CH:39]=[CH:38][O:37][N:36]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C=O)C>[CH2:28]([N:25]1[CH2:24][CH2:23][N:22]([C:17]2[CH:18]=[C:19]3[C:14](=[CH:15][CH:16]=2)[N:13]=[CH:12][N:11]([C:3]2[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=2[CH3:1])[C:6]([NH:34][C:35]2[CH:39]=[CH:38][O:37][N:36]=2)=[O:8])[C:20]3=[O:21])[CH2:27][CH2:26]1)[CH3:29]

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 18102163-IsoxazolamineHCID 686033324-methyl-3-[6-(4-ethylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid

Product 1

HCID 119968603-[6-(4-ethylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]-N-isoxazol-3-yl-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
35 °C

Procedure

To a stirred slurry of 4-methyl-3-[6-(4-ethylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid (0.19 g) and DMF (0.05 ml) in methylene chloride (4 ml) at 35° C. was added thionyl chloride (0.18 ml). The resultant green solution was stirred at 35° C. for 1.5 hours. The reaction mixture was concentrated to give yellow foam. The solid was stirred in methylene chloride (4 ml) at room temperature and 3-aminoisoxazole (0.15 ml) and N,N-diisopropylethylamine (0.25 ml) was added, stirred for 1.5 hours and concentrated. The resultant oil was partitioned between ethyl acetate and a saturated NaHCO3 solution. The aqueous layer was separated and the organic layer washed with brine (5 ml). The organic phase concentrated to give an off-white solid. The solid was triturated with ethyl acetate and collected by filtration to give the title compound as an off-white solid (85 mg); NMR Spectrum: (DMSOd6) 1.05 (3H, t), 2.18 (3H, s), 2.41 (2H, m), 2.55 (4H, m), 3.29 (4H, m), 7.05 (1H, s), 7.50 (1H, s), 7.62 (3H, m), 8.07 (2H, m), 8.13 (1H, s), 8.87 (1H, s), 11.47 (1H, s); Mass Spectrum: M+H+ 459.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give yellow foam
  3. stirringstirred for 1.5 hours
  4. concentrationconcentrated
  5. customThe resultant oil was partitioned between ethyl acetate
  6. customThe aqueous layer was separated
  7. washthe organic layer washed with brine (5 ml)
  8. concentrationThe organic phase concentrated
  9. customto give an off-white solid
  10. customThe solid was triturated with ethyl acetate
  11. filtrationcollected by filtration

Sources & evidence

ORD record
ord-ca23901a763e43da8435b1624d215465
Source dataset
uspto-grants-2010_04
Patent number
US07696215B2

Reaction notes

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