Dimethylformamide → Azd-6703

HRID 2354164Notes

Reaction equation

HRID 2354164 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]([CH3:28])[CH2:24][CH2:23]3)[CH:18]=2)[N:13]=[CH:12]1.CN(C=O)C.S(Cl)(Cl)=O.[CH:38]1([NH2:41])[CH2:40][CH2:39]1>C(Cl)Cl>[CH:38]1([NH:41][C:6](=[O:7])[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)[CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 69828CyclopropylamineHCID 669188194-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid

Product 1

HCID 11373432Azd-6703

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
35 °C

Procedure

To a stirred slurry of 4-methyl-3-[6-(4-methylpiperazin-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 (0.019 ml). The resultant yellow solution was stirred at 35° C. for 2.5 hours. The reaction mixture was concentrated to give a yellow/orange solid. The solid was stirred in methylene chloride (4 ml) at room temperature and cyclopropylamine (0.37 ml) was added, stirred for 10 minutes and concentrated. The resultant solid was partitioned between ethyl acetate (5 ml) and a saturated NaHCO3 solution (2.5 ml). The aqueous layer was separated and the organic layer washed with brine (5 ml). The organic phase concentrated to give a yellow foam and white solid. The mixture was triturated with toluene (5 mL) and filtered to remove the inorganic residues. The toluene solution was concentrated to give a yellow gum which was dissolved in methylene chloride and concentrated (3 times) to give the title compound as a yellow foam (171 mg); NMR Spectrum: (DMSOd6) 0.56 (m, 2H), 0.70 (m, 2H), 2.13 (s, 3H), 2.24 (s, 3H), 2.48 (m, 4H), 2.86 (m, 1H), 3.29 (m, 4H), 7.48 (d, 1H), 7.53 (d, 1H), 7.64 (m, 2H), 7.82 (d, 1H), 7.90 (m, 1H), 8.09 (s, 1H), 8.43 (d, 1H); Mass Spectrum: M+H+ 418.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give a yellow/orange solid
  3. stirringstirred for 10 minutes
  4. concentrationconcentrated
  5. customThe resultant solid was partitioned between ethyl acetate (5 ml)
  6. customThe aqueous layer was separated
  7. washthe organic layer washed with brine (5 ml)
  8. concentrationThe organic phase concentrated
  9. customto give a yellow foam and white solid
  10. customThe mixture was triturated with toluene (5 mL)
  11. filtrationfiltered
  12. customto remove the inorganic residues
  13. concentrationThe toluene solution was concentrated
  14. customto give a yellow gum which
  15. concentrationconcentrated (3 times)

Sources & evidence

ORD record
ord-e1e67f5c196e4354b3c78167b8830bad
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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