Phosphorus oxychloride → N-Isoxazol-3-Yl-4-Methyl-3-[6-(4-Methylpiperazin-1-Yl)-4-Oxo-Quinazolin-3-Yl]benzamide

HRID 641945Notes

Reaction equation

HRID 641945 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][C:8]=1[N:16]1[C:25](=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([N:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)[CH:23]=2)[N:18]=[CH:17]1.[NH2:34][C:35]1[CH:39]=[CH:38][O:37][N:36]=1>N1C=CC=CC=1>[O:37]1[CH:38]=[CH:39][C:35]([NH:34][C:11](=[O:13])[C:10]2[CH:14]=[CH:15][C:7]([CH3:6])=[C:8]([N:16]3[C:25](=[O:26])[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([N:27]5[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]5)[CH:23]=4)[N:18]=[CH:17]3)[CH:9]=2)=[N:36]1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 18102163-IsoxazolamineHCID 669188194-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid

Product 1

HCID 11554076N-Isoxazol-3-Yl-4-Methyl-3-[6-(4-Methylpiperazin-1-Yl)-4-Oxo-Quinazolin-3-Yl]benzamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Phosphorus oxychloride (0.11 ml) was added to a mixture of 4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid (0.30 g), 3-aminoisoxazole (0.12 ml) and pyridine (5 ml) and the resultant suspension was heated to 120° C. for 5 minutes in a microwave (Personal Chemistry Emrys Optimizer with 300 W magnetron). The mixture was evaporated. The residue was partitioned between ethyl acetate and saturated NaHCO3 solution. The organic phase was dried (magnesium sulphate), evaporated and the residue 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 (0.14 g); NMR Spectrum: (DMSOd6) 2.19 (s, 3H), 2.24 (s, 3H), 2.49 (m, 4H), 3.29 (m, 4H), 7.06 (d, 1H), 7.50 (d, 1H), 7.63 (m, 3H), 8.09 (m, 2H), 8.13 (s, 1H), 8.85 (d, 1H), 11.46 (s, 1H); Mass Spectrum: M+H+ 445.

Workup

  1. customThe mixture was evaporated
  2. customThe residue was partitioned between ethyl acetate and saturated NaHCO3 solution
  3. dry with materialThe organic phase was dried (magnesium sulphate)
  4. customevaporated
  5. customthe residue 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-60e44bdf2192407ca0e9a2250f964cf4
Source dataset
uspto-grants-2010_04
Patent number
US07696215B2

Reaction notes

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