tert-Butyl (4-aminophenyl)carbamate → [4-(4-Dimethylamino-quinazolin-2-ylamino)-phenyl]-carbamic acid tert-butyl ester

HRID 1984950Notes

Reaction equation

Cl[C:2]1[N:11]=[C:10]([N:12]([CH3:14])[CH3:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:15]([O:19][C:20](=[O:29])[NH:21][C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=1)([CH3:18])([CH3:17])[CH3:16]>C(Cl)Cl>[C:15]([O:19][C:20](=[O:29])[NH:21][C:22]1[CH:23]=[CH:24][C:25]([NH:28][C:2]2[N:11]=[C:10]([N:12]([CH3:14])[CH3:13])[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)=[CH:26][CH:27]=1)([CH3:18])([CH3:16])[CH3:17]

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of (2-chloro-quinazolin-4-yl)-dimethyl-amine obtained in step B of example 1 (0.5 g, 2.6 mmol) and (4-amino-phenyl)-carbamic acid tert-butyl ester (0.5 g, 2.6 mmol) in CH2Cl2 (2 mL) was heated by Smith Synthesizer at 130° C. for 20 min. The mixture was concentrated to give [4-(4-dimethylamino-quinazolin-2-ylamino)-phenyl]-carbamic acid tert-butyl ester as a pale yellow solid (0.86 g, 87%). The reaction was repeated six times, and the total product combined was 8.5 g. To a solution of above product (8.5 g, 22.4 mmol) in MeOH (250 mL) was added 4 M HCl in dioxane (8.4 ml, 33.6 mmol) dropwise, and the mixture was stirred at ambient temperature for overnight. The mixture was concentrated to give N2-(4-amino-phenyl)-N4,N4-dimethyl-quinazoline-2,4-diamine hydrochloride as a pale pink solid (6.2 g, 87.5%).

Workup

concentrationThe mixture was concentrated

Sources & evidence

ORD record: ord-112cdd2a0f274f819d11b830c2626397
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07544690B2

Reaction notes

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