Thionyl Chloride → HCID 11996859, compound

HRID 641948Notes

Reaction equation

HRID 641948 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[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]([CH:28]([CH3:30])[CH3:29])[CH2:24][CH2:23]3)[CH:18]=2)[N:13]=[CH:12]1.S(Cl)(Cl)=O.[NH2:35][C:36]1[CH:40]=[CH:39][O:38][N:37]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C=O)C>[CH:28]([N:25]1[CH2:26][CH2:27][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:35][C:36]2[CH:40]=[CH:39][O:38][N:37]=2)=[O:7])[C:20]3=[O:21])[CH2:23][CH2:24]1)([CH3:30])[CH3:29]

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 18102163-IsoxazolamineHCID 66918923HCID 66918923, compound

Product 1

HCID 11996859HCID 11996859, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

To a stirred slurry of 4-methyl-3-[6-(4-isopropylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid (0.2 g) and DMF (0.05 ml) in methylene chloride (4 ml) at 35° C. was added thionyl chloride (0.20 ml). The resultant green solution was stirred at 40° C. for 18 hours. The reaction mixture was concentrated to give an orange/brown solid. The solid was stirred in methylene chloride (4 ml) at room temperature and 3-aminoisoxazole (0.15 ml) and N,N-diisopropylethylamine (0.26 ml) was added, stirred for 1.5 hours and concentrated. The resultant oil was partitioned between ethyl acetate and saturated NaHCO3 solution. The aqueous layer was separated and the organic layer washed with brine (5 ml). The organic phase was concentrated to give an orange/brown solid. The residue was purified by column chromatography on a silica column using a 9:1 mixture of ethyl acetate and methanol as eluent to give the title compound as a yellow solid (50 mg); NMR Spectrum: (DMSOd6) 1.04 (d, 6H), 2.18 (s, 3H), 2.62 (m, 4H), 2.68 (m, 1H), 3.28 (m, 4H), 7.05 (s, 1H), 7.49 (s, 1H), 7.66 (m, 3H), 8.08 (m, 2H), 8.12 (s, 1H), 8.86 (s, 1H), 11.47 (s, 1H); Mass Spectrum: M+H+ 473.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give an orange/brown solid
  3. stirringstirred for 1.5 hours
  4. concentrationconcentrated
  5. customThe resultant oil was partitioned between ethyl acetate and saturated NaHCO3 solution
  6. customThe aqueous layer was separated
  7. washthe organic layer washed with brine (5 ml)
  8. concentrationThe organic phase was concentrated
  9. customto give an orange/brown solid
  10. customThe residue was purified by column chromatography on a silica column
  11. additiona 9:1 mixture of ethyl acetate and methanol as eluent

Sources & evidence

ORD record
ord-80b2c4e9102647fab955fe4beacf00a6
Source dataset
uspto-grants-2010_04
Patent number
US07696215B2

Reaction notes

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