1,4-Dioxane hydrochloride → 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-N-methylazetidine-3-carboxamide

HRID 1867768Notes

Reaction equation

HRID 1867768 reaction equation
Cl.O1CCOCC1.[Cl:8][C:9]1[C:10]([F:46])=[C:11]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:44][CH3:45])=[C:23]([CH2:26][N:27]([CH3:43])[C:28]4([C:39]([NH:41][CH3:42])=[O:40])[CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29]4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1>O1CCOCC1>[Cl:8][C:9]1[C:10]([F:46])=[C:11]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:44][CH3:45])=[C:23]([CH2:26][N:27]([CH3:43])[C:28]4([C:39]([NH:41][CH3:42])=[O:40])[CH2:31][NH:30][CH2:29]4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 69047412Tert-butyl 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl) (methyl)amino]-3-[(methylamino)carbonyl]azetidine-1-carboxylate

Product 1

HCID 579798733-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-N-methylazetidine-3-carboxamideYield 130.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of HCl/1,4-dioxan (1/5) (2 ml) was added dropwise to a solution of tert-butyl 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-3-[(methylamino)carbonyl]azetidine-1-carboxylate (310 mg, 0.56 mmol) in 1,4-dioxan (6 ml). The reaction mixture was stirred overnight, then concentrated under reduced pressure. Three triturations in methanol/dichloromethane/diethyl ether afforded the isolation of a hydrochloride salt of 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-N-methylazetidine-3-carboxamide as a solid (336 mg, 100%). 1H NMR Spectrum: (DMSO d6) 2.16 (s, 3H), 2.71 (d, 3H), 3.70 (s, 2H), 3.97 (m, 2H), 4.03 (s, 3H), 4.13 (m, 2H), 7.37 (m, 2H), 7.55 (t, 1H), 7.66 (t, 1H), 8.31 (brs, 1H), 8.90 (brs, 2H), 9.27 (s, 1H), 9.75 (brs, 1H); Mass Spectrum: (M+H)+ 459.

Workup

  1. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f667a2f97c2148fcb5a4df04b6a5b70c
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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