Sodium Carbonate → 3-[5-(6-Amino-5-trifluoromethyl-pyridin-3-yl)-imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-benzamide

HRID 2409570Notes

Reaction equation

I[C:2]1[N:9]2[C:5]([S:6][C:7]([C:10]3[CH:11]=[C:12]([CH:16]=[CH:17][CH:18]=3)[C:13]([NH2:15])=[O:14])=[N:8]2)=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[C:29]([C:34]([F:37])([F:36])[F:35])[C:30]([NH2:33])=[N:31][CH:32]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C(Cl)Cl.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>[NH2:33][C:30]1[N:31]=[CH:32][C:27]([C:2]2[N:9]3[C:5]([S:6][C:7]([C:10]4[CH:11]=[C:12]([CH:16]=[CH:17][CH:18]=4)[C:13]([NH2:15])=[O:14])=[N:8]3)=[N:4][CH:3]=2)=[CH:28][C:29]=1[C:34]([F:37])([F:35])[F:36]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3-(5-Iodo-imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-benzamide (70 mg, 0.18 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-ylamine (75 mg, 0.24 mmol), PdCl2(PPh3)2 (20 mg) and Na2CO3 (60 mg, 0.567 mmol) in dioxane (2 mL) and water (0.5 mL) was heated at 100° C. in a sealed tube for 2 h. The mixture was diluted with DCM (20 mL), washed with sat aq NaHCO3 (2×20 mL) and brine (30 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography and by HPLC to give the desired product (2 mg, 3%). HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=4.26 min, [M+H]+ m/z 405.2; 1H NMR (300 MHz, DMSO) δ 8.84 (s, 1H), 8.34 (s, 1H), 8.30 (s, 1H), 8.22 (s, 1H), 8.06 (t, J=8.6 Hz, 2H), 7.75 (s, 1H), 7.66 (t, J=7.8 Hz, 1H), 7.55 (s, 1H), 6.67 (s, 2H).

Workup

washwashed with sat aq NaHCO3 (2×20 mL) and brine (30 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by column chromatography and by HPLC

Sources & evidence

ORD record: ord-1ec249afdf054b26870ebc1cf4a212a9
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815918B2

Reaction notes

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