Hydrochloric Acid → (S)-1-((S)-1-(3-(7-ethoxy-6-fluoroquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-amine

HRID 339036ノート

反応式

HRID 339036 の反応式
[CH2:1]([O:3][C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][C:10]([C:14]3[N:18]4[CH:19]=[C:20]([C@H:23]([N:28]5[CH2:32][CH2:31][C@@:30]([NH:34]C(=O)OC(C)(C)C)([CH3:33])[CH2:29]5)[C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:22][C:17]4=[N:16][N:15]=3)=[N:11]2)=[CH:6][C:5]=1[F:42])[CH3:2].Cl.O1CCOCC1>C(Cl)Cl.O>[CH2:1]([O:3][C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][C:10]([C:14]3[N:18]4[CH:19]=[C:20]([C@H:23]([N:28]5[CH2:32][CH2:31][C@:30]([CH3:33])([NH2:34])[CH2:29]5)[C:24]([F:26])([F:25])[F:27])[CH:21]=[CH:22][C:17]4=[N:16][N:15]=3)=[N:11]2)=[CH:6][C:5]=1[F:42])[CH3:2]

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86707532tert-butyl (S)-1-((S)-1-(3-(7-ethoxy-6-fluoro quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-ylcarbamate

生成物 1

HCID 71004809(S)-1-((S)-1-(3-(7-ethoxy-6-fluoroquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-amine収率 92.05%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

A solution of tert-butyl (S)-1-((S)-1-(3-(7-ethoxy-6-fluoro quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-ylcarbamate (5.406 g, 9.185 mmol) in DCM (40 mL) was added 4M HCl in dioxane (22.96 mL, 91.85 mmol) and stirred at ambient temperature for 1.5 h. The filtered precipitate was dissolved in water and basified (1N NaOH), extracted with ethyl acetate (3×200 mL), washed with brine (200 mL), dried (MgSO4), filtered concentrated under reduced pressure and the residue purified by flash chromatography (1 column volume DCM, increasing to 10% methanol/DCM over 2 column volumes, holding for 3 column volumes, then switching to 10% [10% NH4OH/Methanol]/DCM for 7 column volumes) to give (S)-1-((S)-1-(3-(7-ethoxy-6-fluoroquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-amine (4.13 g, 8.45 mmol, 92.05% yield). MS APCI (+) m/z 489 (M+1) detected. Specific rotation: [α]20D=−0.87° (c=1.02, MeOH).

後処理

  1. extractionbasified (1N NaOH), extracted with ethyl acetate (3×200 mL)
  2. washwashed with brine (200 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customthe residue purified by flash chromatography (1 column volume DCM
  7. temperatureincreasing to 10% methanol/DCM over 2 column volumes

出典と根拠

ORDレコード
ord-390de3ed46024e0f8e4d15d2c693dbde
出典データセット
uspto-grants-2014_11
特許番号
US08889704B2

反応ノート

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