Potassium Iodide → HCID 66918864, compound

HRID 2354213Notes

Reaction equation

HRID 2354213 reaction equation
[CH:1]1([NH:4][C:5](=[O:25])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[C:22](=[O:23])[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([OH:24])[CH:20]=4)[N:15]=[CH:14]3)[CH:7]=2)[CH2:3][CH2:2]1.C(OC([NH:33][CH2:34][CH2:35]Br)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C.C(OCC)(=O)C>[NH2:33][CH2:34][CH2:35][O:24][C:19]1[CH:20]=[C:21]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][N:13]([C:8]1[CH:7]=[C:6]([CH:11]=[CH:10][C:9]=1[CH3:12])[C:5]([NH:4][CH:1]1[CH2:3][CH2:2]1)=[O:25])[C:22]2=[O:23]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 11404895HCID 11404895, compound

Product 1

HCID 66918864HCID 66918864, compoundYield 48.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-Cyclopropyl-3-(6-hydroxy-4-oxoquinazolin-3(4H)-yl)-4-methylbenzamide (0.621 g), 2-(tert-butoxycarbonylamino)ethyl bromide (0.5 g), potassium carbonate (2.06 g), and potassium iodide (0.025 g) were stirred in DMF (10 ml) at 60° C. for 16 hours. The reaction mixture was diluted with ethyl acetate and washed with water (5×), brine (2×), dried (magnesium sulfate) and concentrated. The resulting solid was dissolved in a solution of 4N HCl in dioxane (4 ml) and methanol (3 ml) and stirred at room temperature for 16 hours. The precipitate was collected by filtration and washed with ethyl acetate. Purification by column chromatography on an ion exchange column (isolute SCX-2 column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) washing with methanol initially and then eluting with a 99:1 mixture of methanol and aqueous ammonia solution gave 3-[6-(2-aminoethoxy)-4-oxoquinazolin-3(4H)-yl]-N-cyclopropyl-4-methylbenzamide (AZ12278502) (0.343 g) as a white solid; NMR Spectrum: (DMSOd6) 0.55 (m, 2H), 0.69 (m, 2H), 1.81 (broad s, 2H), 2.14 (s, 3H), 2.87 (m, 1H), 2.93 (t, 2H), 4.08 (m, 2H), 7.52 (m, 2H), 7.59 (s, 1H), 7.73 (d, 1H), 7.84 (s, 1H), 7.91 (d, 1H), 8.19 (s, 1H), 8.43 (d, 1H); Mass Spectrum: M+H+ 379.

Workup

  1. washwashed with water (5×), brine (2×)
  2. dry with materialdried (magnesium sulfate)
  3. concentrationconcentrated
  4. dissolutionThe resulting solid was dissolved in a solution of 4N HCl in dioxane (4 ml) and methanol (3 ml)
  5. filtrationThe precipitate was collected by filtration
  6. washwashed with ethyl acetate
  7. customPurification by column chromatography on an ion exchange column (isolute SCX-2 column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK)
  8. washwashing with methanol initially
  9. washeluting with a 99:1 mixture of methanol and aqueous ammonia solution

Sources & evidence

ORD record
ord-5ff7ce82aeb44ba9a68ddb969f8a8725
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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