Water → tert-butyl (3R,4R)-4-(6-carbamoyl-5-(6-methylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate

HRID 1396335ノート

反応式

HRID 1396335 の反応式
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[N:13]=2)[CH:3]=1.[NH2:19][C@@H:20]1[CH2:25][CH2:24][O:23][CH2:22][C@@H:21]1[NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30].C(N(CC)C(C)C)(C)C.O>O1CCOCC1.C(OCC)(=O)C>[C:29]([O:28][C:27](=[O:33])[NH:26][C@@H:21]1[C@H:20]([NH:19][C:2]2[N:7]=[N:6][C:5]([C:8](=[O:9])[NH2:10])=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[N:13]=3)[CH:3]=2)[CH2:25][CH2:24][O:23][CH2:22]1)([CH3:32])([CH3:30])[CH3:31]

参加物

7

反応物 4

HCID 962WaterHCID 81531Diisopropylethylamine2 回HCID 68077633tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate2 回HCID 866897076-Chloro-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide

生成物 1

HCID 86689706tert-butyl (3R,4R)-4-(6-carbamoyl-5-(6-methylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate収率 23.7%

試薬・触媒・溶媒 2

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

反応条件

温度
150 °C

実験手順

6-Chloro-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (150 mg, 0.57 mmol) and tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (185 mg, 0.85 mmol) were dissolved in 1,4-dioxane (2.8 mL) and N,N-diisopropylethylamine (0.25 mL, 1.4 mmol). The reaction mixture was stirred at 150° C. for 4 d. Further tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (50 mg, 0.23 mmol) and N,N-diisopropylethylamine (0.04 mL, 0.23 mmol) was added in four portions (every 36 h for 144 h). The mixture was cooled, and then water and ethyl acetate were added. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with sodium chloride solution and dried over sodium sulfate. After concentration, the residue was purified by chromatography (silica, 0 to 7% methanol in dichloromethane) to give {(3R,4R)-4-[6-carbamoyl-5-(6-methyl-pyridin-2-ylamino)-pyridazin-3-ylamino]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester (60 mg, 18%) as a clear amorphous residue. This was 83% pure and was used directly without further purification. MS (EI/CI) m/z: 444 [M+H].

後処理

  1. temperatureThe mixture was cooled
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. concentrationAfter concentration
  6. customthe residue was purified by chromatography (silica, 0 to 7% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-40e947aaa02441078a9d05ad414ad005
出典データセット
uspto-grants-2014_12
特許番号
US08901124B2

反応ノート

読み込み中…