Water → N-Methyl-4-((2-(methylthio)benzo[d]thiazol-6-yl)oxy)picolinamide

HRID 1922219Notes

Reaction equation

[CH3:1][S:2][C:3]1[S:4][C:5]2[CH:11]=[C:10]([OH:12])[CH:9]=[CH:8][C:6]=2[N:7]=1.[CH3:13][NH:14][C:15]([C:17]1[CH:22]=[C:21](Cl)[CH:20]=[CH:19][N:18]=1)=[O:16].O>CN(C=O)C>[CH3:13][NH:14][C:15]([C:17]1[CH:22]=[C:21]([O:12][C:10]2[CH:9]=[CH:8][C:6]3[N:7]=[C:3]([S:2][CH3:1])[S:4][C:5]=3[CH:11]=2)[CH:20]=[CH:19][N:18]=1)=[O:16]

Participants

Conditions

Temperature: 70 °C

Procedure

To the solution of 2-methylsulfanyl-benzothiazol-6-ol (3.76 g, 19.08 mmol, 1.0 eq) in DMF (25 mL), was added CsCO3 (15.54 g, 47.70 mmol, 2.5 eq) at room temperature. After stirring for a while, 4-chloro-pyridine-2-carboxylic acid methylamide (4.86 g, 28.62 mmol, 1.5 eq) was added to the mixture and the mixture was stirred at 70° C. under reflux condenser overnight. After cooling the reaction mixture in ice bath, water (100 mL) was added and the aqueous layer was extracted with ethyl acetate (3×150 mL). The organic layer was dried over sodium sulfate, filtered, and evaporated in vacuo. The crude product was purified using 20 g of ISCO Silica Gel column (0%-50%-80%-100% ethyl acetate-hexane mixture over 45 min 40 mL/min run) to yield 4-(2-methylsulfanyl-benzothiazol-6-yloxy)-pyridine-2-carboxylic acid methylamide (3.88 g, 62%) as a white solid. M+H=332.1

Workup

additionwas added to the mixture
temperatureunder reflux condenser overnight
temperatureAfter cooling the reaction mixture in ice bath
extractionthe aqueous layer was extracted with ethyl acetate (3×150 mL)
dry with materialThe organic layer was dried over sodium sulfate
filtrationfiltered
customevaporated in vacuo
customThe crude product was purified
custom20 g of ISCO Silica Gel column (0%-50%-80%-100% ethyl acetate-hexane mixture over 45 min 40 mL/min run)

Sources & evidence

ORD record: ord-331f32a309454680bb5f7343db8cc8f0
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08173689B2

Reaction notes

Loading…