Cesium carbonate → N-[3-(5-Iodo-imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-benzyl]-methanesulfonamide

HRID 2409567Notes

Reaction equation

Br[C:2]1[S:6][C:5]2=[N:7][CH:8]=[C:9]([I:10])[N:4]2[N:3]=1.[CH3:11][S:12]([NH:15][CH2:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1)(=[O:14])=[O:13].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[I:10][C:9]1[N:4]2[C:5]([S:6][C:2]([C:21]3[CH:22]=[C:17]([CH:18]=[CH:19][CH:20]=3)[CH2:16][NH:15][S:12]([CH3:11])(=[O:14])=[O:13])=[N:3]2)=[N:7][CH:8]=1

Participants

Conditions

Temperature: 115 °C

Procedure

A mixture of 2-bromo-5-iodoimidazo[2,1-b][1,3,4]thiadiazole (0.25 g, 0.757 mmol, 1 eq), (3-methanesulfonylaminomethylphenyl)boronic acid (0.208 g, 0.908 mmol, 1.2 eq), cesium carbonate (0.493 g, 1.514 mmol, 2 eq), Pd(PPh3)2Cl2 (0.053 g, 0.075 mmol, 0.1 eq), 1,4-dioxane (6 mL) and water (6 mL) was heated in a pressure tube at 115° C. for 4 h. Solvents were removed and the slurry obtained was partitioned between water and 10% MeOH in DCM. The organic layer was dried, filtered and evaporated. The residue was purified in an Isolute Flash Si II column (EtOAc) to give the desired product (77 mg, 23%). HPLC-MS (10-95% B in 4 min at 0.5 mL+2 min 100% B, flow 0.8 mL/min, 50° C.): tR=4.04 min, [M+H]+ m/z 435.0.

Workup

customSolvents were removed
customthe slurry obtained
customwas partitioned between water and 10% MeOH in DCM
customThe organic layer was dried
filtrationfiltered
customevaporated
customThe residue was purified in an Isolute Flash Si II column (EtOAc)

Sources & evidence

ORD record: ord-fef5e99258494a0eb5c6768bb0db94ca
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815918B2

Reaction notes

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