4-Methylmorpholine → 2-(((2S,3R)-1-(2-Fluoro-6-(pyrimidin-2-yl)benzoyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

HRID 61199

反応式

HRID 61199 の反応式
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[C:3]=1[C:4]([OH:6])=O.ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.[CH3:35][C@@H:36]1[CH2:41][CH2:40][CH2:39][NH:38][C@@H:37]1[CH2:42][N:43]1[C:51](=[O:52])[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[C:44]1=[O:53]>O1CCOCC1.CCOC(C)=O>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[C:3]=1[C:4]([N:38]1[CH2:39][CH2:40][CH2:41][C@@H:36]([CH3:35])[C@H:37]1[CH2:42][N:43]1[C:51](=[O:52])[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[C:44]1=[O:53])=[O:6]

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 670866032-Fluoro-6-(2-pyrimidinyl)benzoic acidHCID 1177276302-(((2S,3R)-3-Methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

生成物 1

HCID 1177278022-(((2S,3R)-1-(2-Fluoro-6-(pyrimidin-2-yl)benzoyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione収率 15.5%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
80 °C

実験手順

A solution of 2-fluoro-6-(pyrimidin-2-yl)benzoic acid (366 mg, 1.67 mmol), 2-chloro-4,6-dimethoxy-1,3,5-triazine (292 mg, 1.67 mmol), and N-methylmorpholine (421 mg, 4.18 mmol) in anhydrous 1,4-dioxane (10 mL) was stirred at rt under nitrogen for 1.5 h. A solution of 2-(((2S,3R)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione (359 mg, 1.39 mmol) in anhydrous 1,4-dioxane (3 mL) was added at rt. After the addition was completed, the reaction was heated to 80° C. under nitrogen for 5 h. The reaction mixture was cooled to rt, diluted with EtOAc (100 mL), subsequently washed with 0.1 N HCl (100 mL), 0.1 N NaOH (100 mL), and brine (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (0% to 100% EtOAc/hexanes) to afford the title compound as a white foam (99 mg, 15%). ESI MS (M+H) 459.

後処理

  1. additionAfter the addition
  2. temperatureThe reaction mixture was cooled to rt
  3. washsubsequently washed with 0.1 N HCl (100 mL), 0.1 N NaOH (100 mL), and brine (100 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel (0% to 100% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-459f3c8d67f74102a9567f7f3da642cd
出典データセット
uspto-grants-2016_09
特許番号
US09440982B2

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