Potassium Iodide → 3-(((4-(3-Chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl)methyl)(methyl)amino)-1-(2-methoxyethyl)azetidine-3-carboxamide

HRID 1867747Notes

Reaction equation

HRID 1867747 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:29][CH3:30])=[C:16]([CH2:19][N:20]([CH3:28])[C:21]4([C:25]([NH2:27])=[O:26])[CH2:24][NH:23][CH2:22]4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N(C(C)C)CC)(C)C.[CH3:41][O:42][CH2:43][CH2:44]Cl.[I-].[K+]>C(#N)C>[Cl:1][C:2]1[C:3]([F:31])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:29][CH3:30])=[C:16]([CH2:19][N:20]([CH3:28])[C:21]4([C:25]([NH2:27])=[O:26])[CH2:24][N:23]([CH2:44][CH2:43][O:42][CH3:41])[CH2:22]4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 123162-Chloroethyl methyl etherHCID 81531DiisopropylethylamineHCID 579798103-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide

Product 1

HCID 115262383-(((4-(3-Chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl)methyl)(methyl)amino)-1-(2-methoxyethyl)azetidine-3-carboxamideYield 36.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of the hydrochloride salt of 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide (55 mg, 0.11 mmol Example 74), diisopropylethylamine (84 μl, 0.48 mmol), 2-chloroethyl methyl ether (29 μl, 0.32 mmol) and potassium iodide (18 mg, 0.11 mmol) in acetonitrile (0.5 ml) was heated in a microwave at 145° C. for 30 minutes. Purification of the crude product on preparative HPLC (standard basic condition) gave the title product (20 mg, 36%) as a white solid; 1H NMR Spectrum: (CDCl3) 2.41 (s, 3H), 2.76 (t, 2H), 3.34 (s, 3H), 3.36 (d, 2H), 3.44 (t, 2H), 3.66 (d, 2H), 3.96 (s, 3H), 4.00 (s, 2H), 5.38 (brs, 1H), 7.16 (m, 2H), 7.24 (s, 1H), 7.21 (s, 1H), 7.42 (brs, 1H), 7.87 (brs, 1H), 8.01 (s, 1H), 8.75 (m, 1H); Mass Spectrum: (M+H)+ 503.

Workup

  1. customPurification of the crude product on preparative HPLC (standard basic condition)

Sources & evidence

ORD record
ord-07e5fce22e8d4c4db7db666193681991
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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