Lithium Hexamethyldisilazide → (+/-)-10-[(4-Fluoro-2-methoxy-phenyl)-hydroxy-methyl]-2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one

HRID 1520420노트

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HRID 1520420 반응식
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[N:8]=[C:9]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][N:10]3[C:16](=[O:18])[CH:17]=2)=[N:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:29][C:30]1[CH:37]=[CH:36][C:33]([CH:34]=[O:35])=[C:32]([O:38][CH3:39])[CH:31]=1>O1CCCC1>[F:29][C:30]1[CH:37]=[CH:36][C:33]([CH:34]([OH:35])[CH:15]2[CH2:14][CH2:13][CH2:12][CH2:11][N:10]3[C:16](=[O:18])[CH:17]=[C:7]([C:4]4[CH:5]=[CH:6][N:1]=[CH:2][N:3]=4)[N:8]=[C:9]23)=[C:32]([O:38][CH3:39])[CH:31]=1

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 27745374-Fluoro-2-methoxybenzaldehydeHCID 671776292-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one

생성물 1

HCID 44600980(+/-)-10-[(4-Fluoro-2-methoxy-phenyl)-hydroxy-methyl]-2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one수율 62%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-40 °C

실험 절차

To a solution of 0.500 g (2.06 mmol) of 2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-α]azepin-4-one (step 4.1) in dry tetrahydrofuran (20 mL) under argon at −40° C. was added 2.48 mL (2.48 mmol) of lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran). The solution was stirred at −40° C. for 10 min and 0.636 g of 4-fluoro-2-methoxy-benzaldehyde (4.13 mmol) diluted in 5 ml of dry tetrahydrofuran was added. The reaction was allowed to increase to room temperature for 2 h. The mixture was quenched with the addition of a saturated solution of ammonium chloride and extracted with dichloromethane. The organic phase was dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (dichloromethane with 2% of methanol and 0.2% of ammonia) to afford 0.505 g of a white solid (62%).

후처리

  1. additionwas added
  2. temperatureto increase to room temperature for 2 h
  3. customThe mixture was quenched with the addition of a saturated solution of ammonium chloride
  4. extractionextracted with dichloromethane
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (dichloromethane with 2% of methanol and 0.2% of ammonia)

출처 및 근거

ORD 기록
ord-1ec56347ce9d4d8e8d8c67cc5080e8c3
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073914B2

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