Cesium carbonate → tert-butyl 3-(4-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylate

HRID 331014Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][CH:9]=[C:10]([I:11])[C:3]=12.S(O[CH:23]1[CH2:26][N:25]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:24]1)(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.O>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:23]3[CH2:24][N:25]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:26]3)[CH:9]=[C:10]([I:11])[C:3]=12

Participants

Conditions

Temperature: 95 °C

Procedure

To a mixture of 4-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridine (D6) (500 mg, 1.548 mmol) and tert-butyl 3-(tosyloxy)azetidine-1-carboxylate (D100) (558 mg, 1.703 mmol) in DMSO (10 mL) was added cesium carbonate (1513 mg, 4.64 mmol). The final mixture was heated at 80° C. for 4 hours after which the temperature is increase to 95° C. and the mixture heated overnight. The reaction mixture was diluted with water (50 mL) and then extracted with ethyl acetate (50 mL×3). The combined organics were dried over magnesium sulfate and concentrated. The crude was purified on normal phase silica eluting with ethyl acetate and cyclohexane (0-50%) to give the title compound (243 mg). LCMS (A): m/z (M+H)+ 478/480, C15H17BrIN3O2 requires 477/479 (acidic).

Workup

temperaturethe mixture heated overnight
extractionextracted with ethyl acetate (50 mL×3)
dry with materialThe combined organics were dried over magnesium sulfate
concentrationconcentrated
customThe crude was purified on normal phase silica eluting with ethyl acetate and cyclohexane (0-50%)

Sources & evidence

ORD record: ord-40e5db476b6647cdac2ad447f4bf396b
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877742B2

Reaction notes

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