Trichloroacetyl chloride → 4-(Tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid (5-sec-butyl-pyridin-2-yl)-amide

HRID 1920729ノート

反応式

HRID 1920729 の反応式
[CH:1]([C:5]1[CH:6]=[CH:7][C:8]([NH2:11])=[N:9][CH:10]=1)([CH2:3][CH3:4])[CH3:2].C(N(CC)C(C)C)(C)C.ClC(Cl)(Cl)[C:23](Cl)=[O:24].C([O-])(O)=O.[Na+].[N:33]1([C:40]([CH:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[O:41])[CH2:39][CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[CH:1]([C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:23]([N:36]2[CH2:37][CH2:38][CH2:39][N:33]([C:40]([CH:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[O:41])[CH2:34][CH2:35]2)=[O:24])=[N:9][CH:10]=1)([CH2:3][CH3:4])[CH3:2]

参加物

8

反応物 6

HCID 6420Trichloroacetyl chlorideHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 206746695-Sec-butyl-pyridin-2-ylamineHCID 28776660(1,4-Diazepan-1-yl)(tetrahydro-2H-pyran-4-yl)methanone

生成物 1

HCID 591433804-(Tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid (5-sec-butyl-pyridin-2-yl)-amide収率 9%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

To a solution of 90 mg (0.6 mmol) of 5-sec-butyl-pyridin-2-ylamine in DCM (2 mL) was added N,N-diisopropylethylamine (348 μL, 1.2 mmol), followed by 67 μL (0.6 mmol) of trichloroacetylchloride. The reaction mixture was shaken on an orbital shaker for 18 h. Saturated aqueous NaHCO3 solution (3 mL) was added to the reaction mixture. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved in DMF (2 mL) and added to 332 mg (0.6 mmol) of [1,4]diazepan-1-yl-(tetrahydro-pyran-4-yl)-methanone (triple trifluoroacetic acid salt). To this solution 254 mg (2.4 mmol) of Na2CO3 were added and the mixture was heated in a sealed tube at 100° C. for 18 h. The reaction was cooled to room temperature, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by mass-triggered preparative LC-MS to afford 21 mg of 4-(tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid (5-sec-butyl-pyridin-2-yl)-amide. ES−MS: m/z 389;

後処理

  1. dry with materialThe organic layer was dried over Na2SO4
  2. filtrationfiltered
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in DMF (2 mL)
  5. temperatureThe reaction was cooled to room temperature
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by mass-triggered preparative LC-MS

出典と根拠

ORDレコード
ord-5c04c501a01846e58284b4dd33d0f5fc
出典データセット
uspto-grants-2012_05
特許番号
US08173638B2

反応ノート

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