Potassium Iodide → 4-Ethoxy-7-[2-[1-(6-methylpyridazin-3-yl)-4-piperidyl]ethoxy]quinazoline

HRID 468556Notes

Reaction equation

Cl[CH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]2[N:11]=[N:12][C:13]([CH3:16])=[CH:14][CH:15]=2)[CH2:6][CH2:5]1.[OH:17][C:18]1[CH:27]=[C:26]2[C:21]([C:22]([O:28][CH2:29][CH3:30])=[N:23][CH:24]=[N:25]2)=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C>[CH3:16][C:13]1[N:12]=[N:11][C:10]([N:7]2[CH2:8][CH2:9][CH:4]([CH2:3][CH2:2][O:17][C:18]3[CH:27]=[C:26]4[C:21]([C:22]([O:28][CH2:29][CH3:30])=[N:23][CH:24]=[N:25]4)=[CH:20][CH:19]=3)[CH2:5][CH2:6]2)=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 3-[4-(2-chloroethyl)-1-piperidinyl]-6-methyl pyridazine (76 mg, 318 μmol), 7-hydroxy-4-ethoxyquinazoline (100 mg, 526 μmol), potassium carbonate (109 mg, 789 μmol) and potassium iodide (53 mg, 319 μmol) in DMF (5 mL) was heated at 90° C. overnight in an argon atmosphere. The mixture was concentrated, and the residue partitioned between ethyl acetate (100 mL), and water (20 mL). The organic phase was dried (MgSO4), filtered, concentrated and purified by column chromatography (silica), using gradient elution (ethyl acetate-methanol/EA). The combined fractions gave a white solid (22 mg, 18%). The 1H nmr data are recorded in Table 6 below.

Workup

concentrationThe mixture was concentrated
customthe residue partitioned between ethyl acetate (100 mL), and water (20 mL)
dry with materialThe organic phase was dried (MgSO4)
filtrationfiltered
concentrationconcentrated
custompurified by column chromatography (silica)
washelution (ethyl acetate-methanol/EA)

Sources & evidence

ORD record: ord-108ac16d688549d381a0e4efadef53ce
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08624025B2

Reaction notes

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