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 331101노트

반응식

HRID 331101 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
80 °C

실험 절차

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)+

후처리

  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)

출처 및 근거

ORD 기록
ord-470ed9a5fd3f403d9b3c82ce7b4dacb0
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877749B2

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