Sodium hydride → N-(4-chloro-2,6-difluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine

HRID 238104Notes

Reaction equation

HRID 238104 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:23][C:24]1[CH:30]=[C:29]([F:31])[C:27]([NH2:28])=[C:26]([F:32])[CH:25]=1.[H-].[Na+]>CN(C=O)C>[Cl:23][C:24]1[CH:30]=[C:29]([F:31])[C:27]([NH:28][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[C:26]([F:32])[CH:25]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 15125184-Chloro-2,6-DifluoroanilineHCID 117822304-Chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline

Product 1

HCID 5329045N-(4-chloro-2,6-difluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amineYield 61.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Using an analogous procedure to that described in Example 4, 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (246 mg, 0.764 mmol), (prepared as described for the starting material in Example 2c), was reacted with 4-chloro-2,6-difluoroaniline (250 mg, 1.53 mmol), (see WO 97/30035 Example 15), in DMF (9 ml) and in the presence of sodium hydride (60%, 76.5 mg, 1.9 mmol) to give 4-(4-chloro-2,6-difluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (210 mg, 61%).

Workup

  1. custom(prepared

Sources & evidence

ORD record
ord-1706282351e44a6a96c8cda1fd077e00
Source dataset
uspto-grants-2014_02
Patent number
US08642608B2

Reaction notes

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