2,2-Dimethyl-1,3-dioxane-4,6-dione → (3R)-benzyl 3'-methyl-6'-oxo-2',5',6',7'-tetrahydrospiro[cyclopentane-1,4'-pyrazolo[3,4-b]pyridine]-3-carboxylate

HRID 331101ノート

反応式

HRID 331101 の反応式
O=[C:2]1[CH2:6][CH2:5][C@@H:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:3]1.C[C:18]1([CH3:26])[O:23]C(=O)CC(=O)O1.[CH3:27][C:28]1[CH:32]=[C:31]([NH2:33])[NH:30][N:29]=1>CN1CCCC1=O>[CH3:27][C:28]1[NH:29][N:30]=[C:31]2[C:32]=1[C:2]1([CH2:6][CH2:5][C@@H:4]([C:7]([O:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:8])[CH2:3]1)[CH2:26][C:18](=[O:23])[NH:33]2

参加物

5

反応物 3

HCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 86668857(R)-benzyl 3-oxocyclopentanecarboxylateHCID 178418690HCID 178418690、化合物

生成物 1

HCID 136350236(3R)-benzyl 3'-methyl-6'-oxo-2',5',6',7'-tetrahydrospiro[cyclopentane-1,4'-pyrazolo[3,4-b]pyridine]-3-carboxylate

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
80 °C

実験手順

To (R)-benzyl 3-oxocyclopentanecarboxylate (0.4 g, 1.833 mmol) were sequentially added N-methylpyrrolidone (3 mL), 2,2-dimethyl-1,3-dioxane-4,6-dione (0.264 g, 1.833 mmol) and 3-methyl-1H-pyrazol-5-amine (0.178 g, 1.833 mmol) at room temperature. The contents heated to 80° C. (oil bath temp.) for 75 min, and stirred at room temperature for additional 48 hours. The reaction mixture was partitioned between ethyl acetate (40 mL) and 1N hydrogen chloride (15 mL). The ethyl acetate layer was separated and sequentially washed with 1N sodium hydroxide (15 mL), brine (20 mL), dried over sodium sulfate, concentrated and subjected to preparative HPLC (Phenomex Luna AXIA 30×100 mm; 10 min. gradient; solvent A=10% MeOH, 90% H2O, 0.1% TFA, solvent B=90% MeOH, 10% H2O, 0.1% TFA). Fractions corresponding to the desired product were isolated and concentrated. The residue that was obtained was partitioned between dichloromethane (20 mL) and saturated aqueous sodium bicarbonate solution. The dichloromethane layer was separated, dried over sodium sulfate and concentrated to yield a solid (33 mg, 0.097 mmol, 5.31%). It was used as such for the subsequent step without further purification. MS (ESI) m/z 340.16 (M+H)+

後処理

  1. customat room temperature
  2. customThe reaction mixture was partitioned between ethyl acetate (40 mL) and 1N hydrogen chloride (15 mL)
  3. customThe ethyl acetate layer was separated
  4. washsequentially washed with 1N sodium hydroxide (15 mL), brine (20 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customsubjected to preparative HPLC (Phenomex Luna AXIA 30×100 mm; 10 min. gradient; solvent A=10% MeOH, 90% H2O, 0.1% TFA, solvent B=90% MeOH, 10% H2O, 0.1% TFA)

出典と根拠

ORDレコード
ord-470ed9a5fd3f403d9b3c82ce7b4dacb0
出典データセット
uspto-grants-2014_11
特許番号
US08877749B2

反応ノート

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