Acetic Acid → Benzoic acid, 3-[2-(methylthio)thiazolo[5,4-b]pyridin-5-yl]-, ethyl ester

HRID 1615868Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]2[CH:10]=[C:11]([CH:17]=[CH:18][CH:19]=2)[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:6][C:7]=1Br.CCO[C:23]([S-:25])=[S:24].[K+].[C:27](O)(=O)C.IC>CN1C(=O)CCC1.C(OCC)(=O)C>[CH3:27][S:25][C:23]1[S:24][C:7]2[C:2]([N:1]=1)=[CH:3][CH:4]=[C:5]([C:9]1[CH:10]=[C:11]([CH:17]=[CH:18][CH:19]=1)[C:12]([O:14][CH2:15][CH3:16])=[O:13])[N:6]=2

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of ethyl 3-(5-amino-6-bromopyridin-2-yl)benzoate (10.44 g, 32.60 mmol) in NMP (150 mL) was added potassium ethyl xanthogenate (26.14 g, 163.11 mmol) and acetic acid (9.4 mL, 163.11 mmol). The reaction mixture was heated at 150° C. for 16 hours. The mixture was cooled to 50° C. and iodomethane (20.3 mL, 326 mmol) was added. The reaction mixture was further stirred for 30 minutes and partitioned between ethyl acetate and water. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by flash column chromatography using a 85:15 v/v hexane:ethyl acetate as solvent to afford ethyl 3-(2-(methylthio)thiazolo[5,4-b]pyridin-5-yl)benzoate (7.6 g, 70% yield) as a bright brown solid.

Workup

temperatureThe mixture was cooled to 50° C.
custompartitioned between ethyl acetate and water
customThe organic layer was separated
extractionthe aqueous layer was extracted with ethyl acetate
washThe combined organic extracts were washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by flash column chromatography

Sources & evidence

ORD record: ord-fce0464efcc84ff3859465f41707d961
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765747B2

Reaction notes

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