Diisopropylethylamine → Tert-butyl 4-(aminocarbonyl)-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-1-carboxylate

HRID 1867723Notes

Reaction equation

HRID 1867723 reaction equation
Cl.[Cl:2][C:3]1[C:4]([F:24])=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([CH2:20]Cl)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1.[NH2:25][C:26]([C:28]1([NH:41][CH3:42])[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1)=[O:27].CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:25][C:26]([C:28]1([N:41]([CH2:20][C:17]2[CH:18]=[C:19]3[C:14](=[CH:15][C:16]=2[O:22][CH3:23])[N:13]=[CH:12][N:11]=[C:10]3[NH:9][C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([Cl:2])[C:4]=2[F:24])[CH3:42])[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])[CH2:32][CH2:33]1)=[O:27]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 69046774Tert-butyl 4-(aminocarbonyl)-4-(methylamino)piperidine-1-carboxylateHCID 69048319N-(3-chloro-2-fluorophenyl)-6-(chloromethyl)-7-methoxyquinazolin-4-amine hydrochloride

Product 1

HCID 69045783Tert-butyl 4-(aminocarbonyl)-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-1-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(3-chloro-2-fluorophenyl)-6-(chloromethyl)-7-methoxyquinazolin-4-amine hydrochloride (0.30 g, 0.775 mmol) was added over a period of 40 minutes to a stirred solution of tert-butyl 4-(aminocarbonyl)-4-(methylamino)piperidine-1-carboxylate (0.498 g, 1.93 mmol) and DIPEA (0.50 g, 3.89 mmol) in DMF (1 ml) at 120° C. The reaction mixture was stirred for 1 hour, cooled, concentrated and purified by column chromatography on silica eluting with acetonitrile to afford tert-butyl 4-(aminocarbonyl)-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-1-carboxylate (0.35 g, 79%) as a white foam; Mass Spectrum: (M+H)+ 573.

Workup

  1. temperaturecooled
  2. concentrationconcentrated
  3. custompurified by column chromatography on silica eluting with acetonitrile

Sources & evidence

ORD record
ord-e60fe9350bdc49de8b05b7907829fecf
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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