Azetidine → 2-[(E)-2-(5-azetidin-1-yl-2-methyl-2H-[1,2,4]triazol-3-yl)-vinyl]-5,8-dimethyl-[1,2,4]triazolo[1,5-c]pyrimidine

HRID 1055008Notes

Reaction equation

HRID 1055008 reaction equation
Br[C:2]1[N:6]=[C:5](/[CH:7]=[CH:8]/[C:9]2[N:17]=[C:16]3[N:11]([C:12]([CH3:19])=[N:13][CH:14]=[C:15]3[CH3:18])[N:10]=2)[N:4]([CH3:20])[N:3]=1.C1([O-])C=CC=CC=1.[Na+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[NH:71]1[CH2:74][CH2:73][CH2:72]1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd]>[N:71]1([C:2]2[N:6]=[C:5](/[CH:7]=[CH:8]/[C:9]3[N:17]=[C:16]4[N:11]([C:12]([CH3:19])=[N:13][CH:14]=[C:15]4[CH3:18])[N:10]=3)[N:4]([CH3:20])[N:3]=2)[CH2:74][CH2:73][CH2:72]1

Participants

7

Reactant 4

HCID 10422AzetidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 4445035Phenolate SodiumHCID 90018333(E)-2-(2-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)vinyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-c]pyrimidine

Product 1

HCID 727028912-[(E)-2-(5-azetidin-1-yl-2-methyl-2H-[1,2,4]triazol-3-yl)-vinyl]-5,8-dimethyl-[1,2,4]triazolo[1,5-c]pyrimidineYield 63.9%

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of (E)-2-(2-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)vinyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-c]pyrimidine (150 mg, 449 μmol, Eq: 1.00) in dioxane (210.4 ml) was purged with argon, then sodium phenolate (78.2 mg, 673 μmol, Eq: 1.5), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xant-phos) (20.8 mg, 35.9 μmol, Eq: 0.08), tris(dibenzylideneacetone)-dipalladium chloroform complex/Pd2(dba)3CHCl3 (18.6 mg, 18.0 μmol, Eq: 0.04) and azetidine (76.9 mg, 90.5 μl, 1.35 mmol, Eq: 3) were added. The vial was capped and irradiated at 140° C. for 40 minutes in a microwave oven. The crude material was applied on silica gel and purified by flash chromatography over a 20 g silica gel column using ethyl acetate/methanol 0-10% as eluent affording 2-[(E)-2-(5-azetidin-1-yl-2-methyl-2H-[1,2,4]triazol-3-yl)-vinyl]-5,8-dimethyl-[1,2,4]triazolo[1,5-c]pyrimidine (89 mg, 63.9%) as light yellow solid. MS: m/z=311.5 (M+H+), MP: 210.4° C.

Workup

  1. customThe vial was capped
  2. customirradiated at 140° C. for 40 minutes in a microwave oven
  3. custompurified by flash chromatography over a 20 g silica gel column

Sources & evidence

ORD record
ord-efbc5c41af764e128884bf4dd7e2b84c
Source dataset
uspto-grants-2016_07
Patent number
US09394311B2

Reaction notes

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