1-(Azidomethyl)-4-methoxybenzene → [6-[1-(4-Methoxy-benzyl)-1H-[1,2,3]triazol-4-yl]-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 1517070Notes

Reaction equation

HRID 1517070 reaction equation
[C:1]([C:3]1[N:8]=[C:7]([C:9]([N:11]2[CH2:16][CH2:15][CH:14]([N:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[CH2:13][CH2:12]2)=[O:10])[C:6]([CH3:22])=[CH:5][C:4]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=1)#[CH:2].[N:33]([CH2:36][C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=1)=[N+:34]=[N-:35].[Na].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O>CN(C=O)C.O.[Cu]I>[CH3:44][O:43][C:40]1[CH:39]=[CH:38][C:37]([CH2:36][N:33]2[CH:2]=[C:1]([C:3]3[N:8]=[C:7]([C:9]([N:11]4[CH2:16][CH2:15][CH:14]([N:17]5[CH2:21][CH2:20][CH2:19][CH2:18]5)[CH2:13][CH2:12]4)=[O:10])[C:6]([CH3:22])=[CH:5][C:4]=3[C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:31])([F:32])[F:30])[CH:24]=3)[N:35]=[N:34]2)=[CH:42][CH:41]=1

Participants

7

Reactant 3

HCID 109317671-(Azidomethyl)-4-methoxybenzeneHCID 57441142[6-Ethynyl-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneHCID 178519209sodium (L)-ascorbate

Product 1

HCID 57441141[6-[1-(4-Methoxy-benzyl)-1H-[1,2,3]triazol-4-yl]-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneYield 88.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 0.30 g (0.68 mmol) of [6-ethynyl-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 24) and 0.116 g (0.71 mmol) of 1-azidomethyl-4-methoxy-benzene in 3.0 ml of DMF was treated with 0.013 g (0.066 mmol) of (+)-sodium-L-ascorbate and 0.129 g (0.68 mmol) of copper(I) iodide in 1.0 ml of H2O and the reaction was stirred at RT for 2 hours. Then, the solvents were removed by evaporation in high vacuum, the residue was diluted with H2O/NH4OH (25%) and extracted twice with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 95:5) to give 0.363 g (88%) of the title compound as light brown oil. MS: 605.4 (MH).

Workup

  1. customThen, the solvents were removed by evaporation in high vacuum
  2. additionthe residue was diluted with H2O/NH4OH (25%)
  3. extractionextracted twice with CH2Cl2
  4. washthe organic phases were washed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 95:5)

Sources & evidence

ORD record
ord-6c6c8b00fa1747a0b3eef6f54ad4dd08
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

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