Hydrochloric Acid → 3-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide

HRID 1867736Notes

Reaction equation

HRID 1867736 reaction equation
Cl.[NH2:2][C:3]([C:5]1([N:16]([CH2:18][C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][C:28]=2[O:29][CH3:30])[N:25]=[CH:24][N:23]=[C:22]3[NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:33]=2[F:39])[CH3:17])[CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6]1)=[O:4]>O1CCOCC1>[Cl:38][C:34]1[C:33]([F:39])=[C:32]([NH:31][C:22]2[C:21]3[C:26](=[CH:27][C:28]([O:29][CH3:30])=[C:19]([CH2:18][N:16]([CH3:17])[C:5]4([C:3]([NH2:2])=[O:4])[CH2:8][NH:7][CH2:6]4)[CH:20]=3)[N:25]=[CH:24][N:23]=2)[CH:37]=[CH:36][CH:35]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 69047996Tert-butyl 3-(aminocarbonyl)-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-1-carboxylate

Product 1

HCID 579798103-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamideYield 132.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of concentrated hydrochloric acid (5 ml) in 1,4-dioxan (25 ml) was added dropwise to a solution of tert-butyl 3-(aminocarbonyl)-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-1-carboxylate (303 mg, 0.56 mmol) in 1,4-dioxan (6 ml). The reaction mixture was stirred overnight, then concentrated under reduced pressure. The residues were triturated with a mixture of methanol/dichloromethane/diethylether to give the hydrochloride salt of 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide as a solid (330 mg, 100%); 1H NMR Spectrum: (DMSO-d6) 2.19 (s, 3H), 3.73 (s, 2H), 3.95 (brd, 2H), 4.04 (s, 3H), 4.13 (brd, 2H), 7.38 (m, 2H), 7.56 (t, 1H), 7.61 (s, 1H), 7.66 (s, 1H), 7.75 (brs, 1H), 8.92 (s, 1H), 8.92 (brs, 1H), 9.30 (s, 1H), 9.80 (brs, 1H); Mass Spectrum: (M+H)+ 445.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residues were triturated with a mixture of methanol/dichloromethane/diethylether

Sources & evidence

ORD record
ord-5cb7398514b24f7a825e537800d8ef2c
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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