1,4-Butanesultam → 2-sec-Butylamino-6-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-isonicotinic acid methyl ester

HRID 1436573Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([NH:11][CH:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[Na].[S:39]1(=[O:46])(=[O:45])[CH2:44][CH2:43][CH2:42][CH2:41][NH:40]1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([N:40]2[CH2:41][CH2:42][CH2:43][CH2:44][S:39]2(=[O:46])=[O:45])[N:7]=[C:6]([NH:11][CH:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Add 2-sec-butylamino-6-chloro-isonicotinic acid methyl ester (1.0 g, 4.13 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.189 g, 0.207 mmol), 2-(di-tert-butylphosphino) biphenyl (0.123 g, 0.413 mmol) and the sodium salt of [1,2]thiazinane 1,1-dioxide (0.844 g, 5.37 mmol) in toluene (10 mL) to a sealed flask flushed with nitrogen. Heat and stir the sealed flask at 100° C. for 18 h. Cool to room temperature and filter through a bed of filtering agent, and wash with dichloromethane. Concentrate the filtrate and purify (silica gel chromatography, eluting with 20:80 to 30:70 ethyl acetate:hexanes) to give the title compound (0.533 g, 38%).

Workup

temperatureHeat
temperatureCool to room temperature
filtrationfilter through a bed
filtrationof filtering agent
washwash with dichloromethane
concentrationConcentrate the filtrate
custompurify
wash(silica gel chromatography, eluting with 20:80 to 30:70 ethyl acetate:hexanes)

Sources & evidence

ORD record: ord-e2bab62dd9474a13a8579a3665800f2c
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618978B2

Reaction notes

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