1,4-Dioxane → HCID 178501948, compound

HRID 2282316Notes

Reaction equation

HRID 2282316 reaction equation
Br[C:2]1[S:3][C:4]([C:15]2[NH:16][C:17]([NH2:20])=[N:18][N:19]=2)=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=2[Cl:14])[N:6]=1.C[Sn](C)(C)[C:23]1[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30](=[O:33])[O:31][CH3:32])[CH:24]=1.[Cl-].[Li+].O1CCOCC1>[Cu]I.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>[NH2:20][C:17]1[NH:16][C:15]([C:4]2[S:3][C:2]([C:23]3[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30](=[O:33])[O:31][CH3:32])[CH:24]=3)=[N:6][C:5]=2[C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=2[Cl:14])=[N:19][N:18]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 433294Lithium ChlorideHCID 58095130Methyl[4-(trimethylstannyl)pyridin-2-yl]carbamateHCID 178509144HCID 178509144, compound

Product 1

HCID 178501948HCID 178501948, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
120 °C

Procedure

The mixture of 5-[2-bromo-4-(2,4-dichlorophenyl)-1,3-thiazol-5-yl]-4H-1,2,4-triazol-3-amine (0.0300 g, 0.0767 mmol), methyl [4-(trimethylstannyl)pyridin-2-yl]carbamate (0.0362 g, 0.115 mmol), Lithium chloride (9.76 mg, 0.230 mmol), Copper(I) iodide (7.0 mg, 0.037 mmol) and Tetrakis(triphenylphosphine)palladium(0) (7.0 mg, 0.0060 mmol) in dry 1,4-Dioxane (4.0 mL, 51 mmol) was purged with N2 for 5 min, heated to reflux (120° C.) under N2 atmosphere for 3 hours, cooled to r.t. . . . . The mixture was diluted with 10% MeOH-DCM (10 mL), filtered through a short column of Celite/Na2SO4. The filtrate was rotavaped and the residue was chromatographed in a 8 g AnaLogix column using MeOH/DCM (0/100 to 5/95) to give a solid product (0.0084 g, 24% yield). LCMS: (FA) ES+ 462, 464, ES− 460, 462. 1H NMR (400 MHz, d-chloroform & d4-Methanol) 8.21 (s, 1H), 8.05 (s, 1H), 7.30-7.32 (m, 1H), 7.19-7.24 (m, 2H), 7.06-7.09 (m, 1H), 3.54 (s, 3H).

Workup

  1. customwas purged with N2 for 5 min
  2. temperatureheated
  3. temperaturecooled to r.t.
  4. additionThe mixture was diluted with 10% MeOH-DCM (10 mL)
  5. filtrationfiltered through a short column of Celite/Na2SO4
  6. customthe residue was chromatographed in a 8 g AnaLogix column

Sources & evidence

ORD record
ord-8ed8d9728ba84de0979694aadfc38b1c
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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