2-Butynoic acid → N-(4-((3-bromophenyl)amino)-6-quinazolinyl)-2-butynamide

HRID 1698960Notes

Reaction equation

[C:1]([OH:6])(=O)[C:2]#[C:3][CH3:4].Cl.CN(C)CCCN=C=NCC.[NH2:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][N:24]=[C:23]2[NH:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Br:37])[CH:32]=1>CN(C=O)C>[Br:37][C:33]1[CH:32]=[C:31]([NH:30][C:23]2[C:22]3[C:27](=[CH:28][CH:29]=[C:20]([NH:19][C:1](=[O:6])[C:2]#[C:3][CH3:4])[CH:21]=3)[N:26]=[CH:25][N:24]=2)[CH:36]=[CH:35][CH:34]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of 2-butynoic acid (196 mg, 2.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (385 mg, 2.0 mmol) in DMF (5 mL) stirring at 25° C. for 20 minutes was added 6-amino-4-[(3-bromophenyl)amino]quinazoline (316 mg, 1.0 mmol). The resulting solution was stirred under N2 at 25° C. for 14 hours further 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (206 mg, 1.0 mmol) and 2-butynic acid (82 mg, 1.0 mmol) were. After another 8 hours further, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (197 mg, 1.0 mmol) and the acid (93 mg, 1.0 mmol) were added to the reaction. After stirring at 25° C. a further 12 hours, the reaction was quenched with water. The yellow precipitate was collected, sonicated with acetone, treated with triethyl amine and purified by preparative tlc on silica, eluting with 1:1 EtOAc/acetone. The desired product was isolated as a yellow solid (20 mg, 4.7%), mp 281-283° C.

Workup

customthe reaction was quenched with water
customThe yellow precipitate was collected
customsonicated with acetone
additiontreated with triethyl amine
custompurified by preparative tlc on silica
washeluting with 1:1 EtOAc/acetone

Sources & evidence

ORD record: ord-da35901dcb2742009bb9f842fe5cb0ef
Source dataset: uspto-grants-2002_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06344459B1

Reaction notes

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