Lithium iodide → N2-({4-[(3-chloro-2-fluorophenyl)amino]-7-hydroxyquinazolin-6-yl}methyl)-N1,N1-dimethylglycinamide

HRID 1867721Notes

Reaction equation

HRID 1867721 reaction equation
[Cl:1][C:2]1[C:3]([F:29])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:27]C)=[C:16]([CH2:19][NH:20][CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.[I-].[Li+]>N1C(C)=CC(C)=CC=1C>[Cl:1][C:2]1[C:3]([F:29])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([OH:27])=[C:16]([CH2:19][NH:20][CH2:21][C:22]([N:24]([CH3:25])[CH3:26])=[O:23])[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 66321Lithium iodideHCID 69048326HCID 69048326, compound

Product 1

HCID 136355267N2-({4-[(3-chloro-2-fluorophenyl)amino]-7-hydroxyquinazolin-6-yl}methyl)-N1,N1-dimethylglycinamideYield 56.9%

Reagents, catalysts & solvents 1

HCID 79532,4,6-TrimethylpyridineSolvent

Conditions

Temperature
130 °C

Procedure

N-(3-chloro-2-fluorophenyl)-6-(chloromethyl)-7-methoxyquinazolin-4-amine (0.21 g, 0.60 mmol) was added to a stirred solution of N1,N1,N2-trimethylglycinamide (Me2N-Gly-Nme) (0.348 g, 1.81 mmol) and DIPEA (0.234 g, 1.81 mmol) in dimethylformamide (1 ml) at 140° C., over a period of 5 minutes. The reaction mixture was stirred for 5 minutes, cooled to room temperature and purified by preparative LCMS (standard acidic system) to give N2-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)-N1,N1-dimethylglycinamide (0.193 g, 74.2%) as a white solid. 1H NMR Spectrum: (DMSO-d6) 2.27 (s, 3H), 2.80 (s, 3H), 2.98 (s, 3H), 3.71 (s, 2H), 3.94 (s, 3H), 7.19 (s, 1H), 7.27 (t, 1H), 7.47-7.52 (m, 2H), 8.30 (s, 1H), 8.43 (s, 1H), 9.85 (s, 1H); Mass Spectrum: (M+H)+ 432. Solid N2-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)-N1,N1-dimethylglycinamide (0.150 g, 0.348 mmol) was added over a period of 1 minute to a stirred solution of anhydrous lithium iodide (0.232 g, 1.74 mmol) in 2,4,6-collidine (0.5 ml) at 130° C., previously stirred for 30 minutes at 130° C. The reaction mixture was allowed to stir for 5 hours, cooled, concentrated and purified by preparative LCMS (standard acidic system) to afford N2-({4-[(3-chloro-2-fluorophenyl)amino]-7-hydroxyquinazolin-6-yl}methyl)-N1,N1-dimethylglycinamide (0.080 g, 55.2%) as an orange foam; Mass Spectrum: (M+H)+ 418.

Workup

  1. stirringto stir for 5 hours
  2. temperaturecooled
  3. concentrationconcentrated
  4. custompurified by preparative LCMS (standard acidic system)

Sources & evidence

ORD record
ord-608b33df8ac04f7184e54a5568521e6c
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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