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 1517070노트

반응식

HRID 1517070 반응식
[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

참가 물질

7

반응물 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

생성물 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)-methanone수율 88.3%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-6c6c8b00fa1747a0b3eef6f54ad4dd08
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08227613B2

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