N-Iodosuccinimide → 4-Tert-Butyl-2-(4-methyl-benzoylamino)-4H-pyrrolo[2,3-d]thiazole-6-carboxylic acid ethyl ester

HRID 1594224Notes

Reaction equation

[CH3:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([N:8]=[C:9]=[S:10])=[O:7])=[CH:4][CH:3]=1.[CH2:13]([O:15][C:16]([C:18]1[CH:22]=[C:21]([NH2:23])[N:20]([C:24]([CH3:27])([CH3:26])[CH3:25])[CH:19]=1)=[O:17])[CH3:14].IN1C(=O)CCC1=O.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>C1COCC1>[CH2:13]([O:15][C:16]([C:18]1[C:22]2[S:10][C:9]([NH:8][C:6](=[O:7])[C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:12][CH:11]=3)=[N:23][C:21]=2[N:20]([C:24]([CH3:25])([CH3:27])[CH3:26])[CH:19]=1)=[O:17])[CH3:14]

Participants

Conditions

Temperature: 0 °C

Procedure

4-Methyl-benzoyl isothiocyanate (4.5 ml, 29.5 mmol) was added neat, via syringe under N2 blanket, to a stirred solution of 5-amino-1-tert-butyl-1H-pyrrole-3-carboxylic acid ethyl ester (5.6 g, 26.6 mmol) in anhydrous THF (270 ml), and brought to reflux for 1.5 hours. The solution was chilled to 0° C., then neat N-iodosuccinimide (6.6 g, 29.3 mmol) was added, and the solution was allowed to stir and warm to ambient temperature overnight for 16 hours. Reaction was slowly poured into a stirred 10% (w/v) sodium metabisulfite aqueous solution (200 ml), then extracted with ethyl acetate, dried (MgSO4), and flash chromatographed (silica gel, 25% (v/v) EtOAc/hexanes). Isolated product was crystallized from ethyl acetate/hexanes to afford 4.2 g (41%) of white powder, mp. 200-201° C. MS:M+H=386.

Workup

temperatureto reflux for 1.5 hours
temperaturewarm to ambient temperature overnight for 16 hours
customReaction
extractionextracted with ethyl acetate
dry with materialdried (MgSO4), and flash
customchromatographed (silica gel, 25% (v/v) EtOAc/hexanes)
customIsolated product was crystallized from ethyl acetate/hexanes

Sources & evidence

ORD record: ord-228e9fe95875475bbc319d811bba653a
Source dataset: uspto-grants-2007_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07300949B2

Reaction notes

Loading…