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 1517070ノート

反応式

HRID 1517070 の反応式
[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

参加物

7

反応物 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

生成物 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)-methanone収率 88.3%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-6c6c8b00fa1747a0b3eef6f54ad4dd08
出典データセット
uspto-grants-2012_07
特許番号
US08227613B2

反応ノート

読み込み中…