Water → 4-[4-(5-Iodo-imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-2-methoxy-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2409543Notes

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.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([O:24][C:25]2[CH:30]=[CH:29][C:28](B3OC(C)(C)C(C)(C)O3)=[CH:27][C:26]=2[O:40][CH3:41])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C([O-])([O-])=O.[Cs+].[Cs+].O>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>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([O:24][C:25]2[CH:30]=[CH:29][C:28]([C:2]3[S:6][C:5]4=[N:7][CH:8]=[C:9]([I:10])[N:4]4[N:3]=3)=[CH:27][C:26]=2[O:40][CH3:41])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

Conditions

Temperature: 115 °C

Procedure

To a suspension of 2-bromo-5-iodoimidazo[2,1-b][1,3,4]thiadiazole (0.262 g, 0.794 mmol, 1 eq) in 1,4-dioxane (13 mL), 4-[2-Methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester (0.413 g, 0.953 mmol, 1.2 eq), Cs2CO3 (0.517 g, 1.588 mmol, 2 eq), dichlorobis(triphenylphosphine)palladium(II) (0.056 g, 0.079 mmol, 0.1 eq) and water (6 ml) were added. The resulting mixture was heated at 115° C. overnight. Solvents were removed and the crude was purified in an (solute Flash Si II column (25 g silica gel, 10%-21% EtOAc in c-hexane) to give the desired product (0.21 g). HPLC-MS (10-95% B in 4 min at 0.5 mL+2 min 100% B, flow 0.8 mL/min, 50° C.): tR=4.98 min, [M+H]+ m/z 557.1.

Workup

additionwere added
customSolvents were removed
customthe crude was purified in an (solute Flash Si II column (25 g silica gel, 10%-21% EtOAc in c-hexane)

Sources & evidence

ORD record: ord-f1891527653f4fe894da7dd0aa8f58dc
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815918B2

Reaction notes

Loading…