Cesium carbonate → tert-Butyl methyl(1-(5-(thiophen-2-yl)tetrazolo[1,5-a]pyrazin-8-yl)azetidin-3-yl)carbamate

HRID 535711Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

A 3 L round bottom flask was charged with tert-butyl (1-(5-bromotetrazolo[1,5-a]pyrazin-8-yl)azetidin-3-yl)(methyl)carbamate (50 g, 0.13 mol), thiophene-2-boronic acid (22 g, 0.17 mol), tetrakis(triphenylphosphine)palladium(0) (5.0 g, 4.3 mmol), Cs2CO3 (50 g, 0.15 mol), 1,4-dioxane (1.5 L) and water (500 mL). After the air was purged by bubbling N2 into the solution, the resulting solution was stirred at 80° C. under N2 for 14 h. Work-up: the reaction mixture was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with 0-25% ethyl acetate in CH2Cl2, and then crystallized from methanol, to afford 35 g (70%) of the product as a yellow solid.

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 with 0-25% ethyl acetate in CH2Cl2
customcrystallized from methanol

Sources & evidence

ORD record: ord-4d7a96800acf468bb5fcb2395967e276
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08859550B2

Reaction notes

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