Hydrochloric Acid → HCID 178519793、化合物

HRID 2271549ノート

反応式

HRID 2271549 の反応式
[F:1][C@@H:2]1[CH2:6][CH2:5][N:4]([CH2:7][C@H:8]2[CH2:13][CH2:12][C@H:11]([NH:14][C:15](=O)OC(C)(C)C)[CH2:10][CH2:9]2)[CH2:3]1.Cl.[Br:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[N:30]=[CH:29][C:28]([C:34]([CH:36]1[CH2:38][CH2:37]1)=[O:35])=C2Cl.C([O-])([O-])=O.[K+].[K+].C(N(CC)C(C)C)(C)C>C1COCC1.O1CCOCC1.O>[Br:23][C:24]1[CH:33]=[C:32]2[C:31](=[CH:26][CH:25]=1)[N:30]=[CH:29][C:28]([C:34]([CH:36]1[CH2:38][CH2:37]1)=[O:35])=[C:15]2[NH:14][C@H:11]1[CH2:10][CH2:9][C@H:8]([CH2:7][N:4]2[CH2:5][CH2:6][C@@H:2]([F:1])[CH2:3]2)[CH2:13][CH2:12]1

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 66715111(6-Bromo-4-chloroquinolin-3-yl)(cyclopropyl)methanoneHCID 178453933HCID 178453933、化合物

生成物 1

HCID 178519793HCID 178519793、化合物収率 52.4%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
65 °C

実験手順

To a solution of tert-butyl (trans-4-(((R)-3-fluoropyrrolidin-1-yl)methyl)cyclohexyl)carbamate (265 mg, 0.88 mmol) in THF (6 mL) was added aqueous 6N HCl (6 mL) and water (6 mL) and the reaction mixture was heated at 65° C. for 3 h. The reaction mixture was cooled to room temperature, diluted with satd. aq. sodium bicarbonate (50 mL) and 1 M aqueous sodium hydroxide (50 mL) and extracted with a mixture of CHCl3/isopropanol (3:1). The combined organic layers were dried over anhydrous sodium sulfate and concentrated to afford a white semisolid. The residue was dissolved in dioxane followed by the addition of (6-bromo-4-chloroquinolin-3-yl)(cyclopropyl)methanone (225 mg, 0.724 mmol), K2CO3 (415 mg, 3.0 mmol), and N,N-diisopropylethylamine (0.39 mL, 3.0 mmol) and the resultant suspension was heated at 80° C. for 16 h. The reaction was cooled to room temperature, diluted with satd. aq. NaHCO3 and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated. Purification by column chromatography (silica, 0-20% methanol/dichloromethane) afforded the desired product (180 mg, 52%) as an off-white solid. ESI MS m/z 474 [C24H29BrFN3O+H]+

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. additiondiluted with satd
  3. extractionaq. sodium bicarbonate (50 mL) and 1 M aqueous sodium hydroxide (50 mL) and extracted with a mixture of CHCl3/isopropanol (3:1)
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto afford a white semisolid
  7. temperatureThe reaction was cooled to room temperature
  8. additiondiluted with satd
  9. extractionaq. NaHCO3 and extracted with ethyl acetate
  10. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  11. concentrationconcentrated
  12. customPurification by column chromatography (silica, 0-20% methanol/dichloromethane)

出典と根拠

ORDレコード
ord-01e23f7982df48a0a4ba51a00903d841
出典データセット
uspto-grants-2015_09
特許番号
US09120749B2

反応ノート

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