4-Methylmorpholine → N-[4-(3-Bromo-phenylamino)-quinazolin-6-yl]-2-isobutyldisulfanyl-acetamide

HRID 1069019Notes

Reaction equation

[CH2:1]([S:5][S:6][CH2:7][C:8]([OH:10])=O)[CH:2]([CH3:4])[CH3:3].ClC(OCC(C)C)=O.CN1CCOCC1.[NH2:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[N:33]=[CH:32][N:31]=[C:30]2[NH:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([Br:44])[CH:39]=1>O1CCCC1.C(Cl)Cl.CO>[Br:44][C:40]1[CH:39]=[C:38]([NH:37][C:30]2[C:29]3[C:34](=[CH:35][CH:36]=[C:27]([NH:26][C:8](=[O:10])[CH2:7][S:6][S:5][CH2:1][CH:2]([CH3:3])[CH3:4])[CH:28]=3)[N:33]=[CH:32][N:31]=2)[CH:43]=[CH:42][CH:41]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 3.0 grams of disulfide acid from Example 76 in 50 mL of tetrahydrofuran was cooled in an ice bath. A 2.1 mL portion of isobutyl chloroformate followed by a 1.8 mL portion of N-methyl morpholine were added. After stirring for 5 minutes at 0° C., 0.85 grams of 6-amino 4-(3-bromoanilino)quinazoline was added. The mixture was stirred for 3 hours at 0° C. and then allowed to warm to room temperature. The reaction was quenched with water and the tetrahydrofuran was evaporated under vacuum. Addition of methylene chloride followed by washing the methylene chloride layer with water and evaporation of the solvent gave a crude product. Silica gel chromatography with methanol in methylene chloride gave 0.15 grams white solid of product.

Workup

additionwere added
stirringThe mixture was stirred for 3 hours at 0° C.
temperatureto warm to room temperature
customThe reaction was quenched with water
customthe tetrahydrofuran was evaporated under vacuum
additionAddition of methylene chloride
washby washing the methylene chloride layer
customwith water and evaporation of the solvent
customgave a crude product

Sources & evidence

ORD record: ord-89ddb9f9b8764443acbb5fe3cf150cca
Source dataset: uspto-grants-2001_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06251912B1

Reaction notes

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