1,4-Dioxane → tert-butyl 4-(5-bromo-1,3,4-thiadiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 579320Notes

Reaction equation

CC1(C)C(C)(C)OB([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]=2)O1.[Br:23][C:24]1[S:25][C:26](Br)=[N:27][N:28]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Br:23][C:24]1[S:25][C:26]([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:11][CH:10]=2)=[N:27][N:28]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a 5 mL microwave vial was added tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (247 mg, 0.8 mmol), 2,5-dibromo-1,3,4-thiadiazole (98 mg, 0.4 mmol), K3PO4 (212 mg, 1.0 mmol), Pd(PPh3)4 (23 mg, 0.02 mmol), 1,4-dioxane (2 mL), and water (0.4 mL). The mixture was purged with N2 for 10 min, then heated to 100° C. in the microwave for 1 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography (EtOAc/Heptane) to afford 64 mg (46%) of tert-butyl 4-(5-bromo-1,3,4-thiadiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate: MS (M+2)=348.1; 1H NMR (400 MHz, CHLOROFORM-d) δ 6.46 (td, J=3.0, 1.9 Hz, 1H), 4.15 (d, J=3.0 Hz, 2H), 3.64 (t, J=5.6 Hz, 2H), 2.73 (m, 2H), 1.49 (s, 9H).

Workup

customThe mixture was purged with N2 for 10 min
additionThe mixture was diluted with EtOAc
washwashed with water and brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography (EtOAc/Heptane)

Sources & evidence

ORD record: ord-a01868513b344c339eefcf02f03acbe5
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040712B2

Reaction notes

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