Potassium Iodide → HCID 86619731, compound

HRID 1879953Notes

Reaction equation

Cl[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[Cl:10][C:11]1[C:12]([F:37])=[C:13]([CH:34]=[CH:35][CH:36]=1)[NH:14][C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:32][CH3:33])=[C:22]([O:25][CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[CH:23]=2)[N:18]=[CH:17][N:16]=1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O>[C:6]([O:5][C:3](=[O:4])[CH2:2][N:29]1[CH2:30][CH2:31][CH:26]([O:25][C:22]2[CH:23]=[C:24]3[C:19](=[CH:20][C:21]=2[O:32][CH3:33])[N:18]=[CH:17][N:16]=[C:15]3[NH:14][C:13]2[CH:34]=[CH:35][CH:36]=[C:11]([Cl:10])[C:12]=2[F:37])[CH2:27][CH2:28]1)([CH3:9])([CH3:8])[CH3:7]

Participants

Conditions

Temperature: 70 °C

Procedure

Tert-butyl chloroacetate (1.43 ml, 10 mmol) was added dropwise to a mixture of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline (4.02 g, 10 mmol), potassium iodide (1.66 g, 10 mmol) and potassium carbonate (1.66 g, 12 mmol) in dimethylacetamide (50 ml). The mixture was heated at 70° C. for one hour. After evaporation of the solvents under vacuum, the residue was triturated in water. The resulting solid was filtered, washed with water and purified by chromatography on silica gel (eluant: 2% 7N methanolic ammonia in dichloromethane) to give tert-butyl[4-({4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl}oxy)piperidin-1-yl]acetate as a white solid (3.0 g, 60%).

Workup

customAfter evaporation of the solvents under vacuum
customthe residue was triturated in water
filtrationThe resulting solid was filtered
washwashed with water
custompurified by chromatography on silica gel (eluant: 2% 7N methanolic ammonia in dichloromethane)

Sources & evidence

ORD record: ord-58f4e3beefda40c09d41b8f1e6f73a5e
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318752B2

Reaction notes

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