Acetic Acid → Tert-butyl 4-(7-bromo-2-(4-sulfamoylphenylamino)quinazolin-8-yloxy)piperidine-1-carboxylate

HRID 2079621Notes

Reaction equation

CC([O-])(C)C.[K+].[Br:7][C:8]1[C:17]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]2)=[C:16]2[C:11]([CH:12]=[N:13][C:14](Cl)=[N:15]2)=[CH:10][CH:9]=1.[NH2:33][C:34]1[CH:39]=[CH:38][C:37]([S:40]([NH2:43])(=[O:42])=[O:41])=[CH:36][CH:35]=1.CC(O)=O>CC(O)C>[Br:7][C:8]1[C:17]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]2)=[C:16]2[C:11]([CH:12]=[N:13][C:14]([NH:33][C:34]3[CH:39]=[CH:38][C:37]([S:40](=[O:42])(=[O:41])[NH2:43])=[CH:36][CH:35]=3)=[N:15]2)=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 105 °C

Procedure

Solid KOtBu (442 mg, 3.95 mmole) was added to a solution of tert-butyl 4-(7-bromo-2-chloroquinazolin-8-yloxy)piperidine-1-carboxylate (500 mg, 1.13 mmole) and 4-aminobenzenesulfonamide (777 mg, 4.62 mmole) in IPA (15 mL). The reaction was sealed and heated to 105° C. with stirring. After 2.5 hours, AcOH was added to the reaction to pH 4 and the reaction was evaporated to a solid. The crude product was dissolved in DMSO (15 mL) and purified by prep. HPLC to give 241 mg of product in 37% yield (417 mmole).

Workup

customThe reaction was sealed
customthe reaction was evaporated to a solid
dissolutionThe crude product was dissolved in DMSO (15 mL)
custompurified by prep

Sources & evidence

ORD record: ord-ca066d03a754464296adc8666d4975aa
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07932262B2

Reaction notes

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