Cesium carbonate → tert-Butyl 4-(5-(thiophen-2-yl)tetrazolo[1,5-a]pyrazin-8-yl)piperazine-1-carboxylate

HRID 1045734Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

A 1 L round bottom flask was charged with tert-butyl 4-(5-bromotetrazolo[1,5-a]pyrazin-8-yl)piperazine-1-carboxylate (50 g, 0.13 mol), thiophene-2-boronic acid (22 g, 0.17 mol), tetrakis(triphenylphosphine)palladium(0) (7.5 g, 6.5 mmol), Cs2CO3 (51 g, 0.16 mol), 1,4-dioxane (600 mL) and H2O (240 mL). After the air was purged by bubbling N2 into the solution, the resulting solution was stirred at 80° C. under N2 for 10 h. Work-up: the reaction mixture was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluted with CH2Cl2, and then crystallized from methanol, to afford 35 g (70%) of the product as a yellow solid. MS m/z: 388 (M+H+).

Workup

customAfter the air was purged
customby bubbling N2 into the solution
concentrationthe reaction mixture was concentrated in vacuo
customThe residue was purified by flash column chromatography on silica gel
washeluted with CH2Cl2
customcrystallized from methanol

Sources & evidence

ORD record: ord-0c9a4c57868b432cb99a875432e257bc
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569300B2

Reaction notes

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