Acetone Cyanohydrin → HCID 178495760, 화합물

HRID 714425노트

반응식

HRID 714425 반응식
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:10]([CH2:19][CH2:20][O:21][CH3:22])[C:11](=[O:18])[C:12]([C:15]([OH:17])=O)=[CH:13][N:14]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[C:23](Cl)(=[O:27])[C:24](Cl)=O.C[C:30](=[O:38])[CH2:31][C:32](=O)[CH2:33][CH2:34][CH2:35]C.C(N(CC)CC)C.OC(C)(C)C#N>ClCCl.CN(C)C=O>[F:8][C:6]1[CH:5]=[C:4]([C:9]2[N:10]([CH2:19][CH2:20][O:21][CH3:22])[C:11](=[O:18])[C:12]([C:15]([C:24]3[C:23](=[O:27])[CH:33]4[CH2:32][CH:31]([CH2:35][CH2:34]4)[C:30]=3[OH:38])=[O:17])=[CH:13][N:14]=2)[CH:3]=[C:2]([F:1])[CH:7]=1

참가 물질

8

반응물 5

HCID 6406Acetone CyanohydrinHCID 8471Triethylamine2회HCID 65578Oxalyl chlorideHCID 841922,4-OctanedioneHCID 679550472-(3,5-Difluorophenyl)-1,6-dihydro-1-(2-methoxyethyl)-6-oxo-5-pyrimidinecarboxylic acid2회

생성물 1

HCID 178495760HCID 178495760, 화합물

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매

실험 절차

To 2-(3,5-difluorophenyl)-1,6-dihydro-1-(2-methoxyethyl)-6-oxo-5-pyrimidinecarboxylic acid (i.e. the product from Example 9, Step D) (0.25 g, 0.81 mmol) in 10 mL of dichloromethane was added oxalyl chloride (0.21 g, 1.6 mmol) and one drop of N,N-dimethylformamide. The reaction mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure. The remaining crude oil was re-dissolved in dichloromethane (10 mL) and then treated with bicycle[3.2.1]octane-2,4-dione (0.12 g, 0.88 mmol) (prepared according to U.S. Pat. No. 6,815,563) and triethylamine (0.16 g, 1.6 mmol). After 30 min at room temperature, a catalytic amount of 2-hydroxy-2-methyl-propanenitrile (0.0075 g, 0.088 mmol) and triethylamine (0.16 g, 1.6 mmol) were added and the reaction mixture was stirred at ambient temperature over night. The reaction mixture was then concentrated under reduced pressure and purified by medium pressure liquid chromatography on silica gel eluting with 0 to 10% methanol in chloroform to provide 0.180 g of the title compound (also known as 3-[[2-(3,5-difluorophenyl)-1,6-dihydro-1-(2-methoxyethyl)-6-oxo-5-pyrimidinyl]carbonyl]biciclo[3.2.1]octane-2,4-dione), a compound of the present invention, as a solid.

후처리

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe remaining crude oil was re-dissolved in dichloromethane (10 mL)
  3. customprepared
  4. waitAfter 30 min at room temperature
  5. stirringthe reaction mixture was stirred at ambient temperature over night
  6. concentrationThe reaction mixture was then concentrated under reduced pressure
  7. custompurified by medium pressure liquid chromatography on silica gel eluting with 0 to 10% methanol in chloroform

출처 및 근거

ORD 기록
ord-6f897db8edeb41a28db0e5f16591bb0c
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187432B2

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