Dimethylformamide → N-isoxazol-5-yl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamide

HRID 641947Notes

Reaction equation

HRID 641947 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]([CH3:28])[CH2:24][CH2:23]3)[CH:18]=2)[N:13]=[CH:12]1.CN(C=O)C.S(Cl)(Cl)=O.[NH2:38][C:39]1[O:43][N:42]=[CH:41][CH:40]=1>C(Cl)Cl.N1C=CC=CC=1>[O:43]1[C:39]([NH:38][C:6](=[O:8])[C:5]2[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([N:11]3[C:20](=[O:21])[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([N:22]5[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]5)[CH:18]=4)[N:13]=[CH:12]3)[CH:4]=2)=[CH:40][CH:41]=[N:42]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 845915-AminoisoxazoleHCID 669188194-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid

Product 1

HCID 11996858N-isoxazol-5-yl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamideYield 19.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
45 °C

Procedure

To a stirred slurry of 4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid (0.3 g) and DMF (0.05 ml) in methylene chloride (30 ml) at 35° C. was added thionyl chloride (0.3 ml). The resultant yellow solution was stirred at 45° C. for 1.5 hours. The reaction mixture was concentrated to give a yellow/orange solid. The solid was stirred in methylene chloride (30 ml) at room temperature with 5-aminoisoxazole (0.11 g) and pyridine (0.2 ml) for 18 hours. The reaction mixture was washed with saturated NaHCO3 solution, brine and concentrated. The residue was purified by column chromatography on a silica column using initially methylene chloride and then a 9:1 mixture of methylene chloride and methanol as eluent. There was thus obtained the title compound (70 mg); NMR Spectrum: (DMSOd6) 2.19 (s, 3H), 2.25 (s, 3H), 2.49 (m, 4H), 3.30 (m, 4H), 6.43 (d, 1H), 7.50 (d, 1H), 7.62 (s, 1H), 7.65 (m, 2H), 8.08 (s, 1H), 8.10 (m, 1H), 8.13 (s, 1H), 8.50 (d, 1H), 12.04 (s, 1H); Mass Spectrum: M+H+ 444.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give a yellow/orange solid
  3. washThe reaction mixture was washed with saturated NaHCO3 solution, brine
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on a silica column
  6. additiona 9:1 mixture of methylene chloride and methanol as eluent

Sources & evidence

ORD record
ord-fb22fc9198114efe9a1daef41268d149
Source dataset
uspto-grants-2010_04
Patent number
US07696215B2

Reaction notes

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