Dimethyl Sulfoxide → (2R,4S,4aS)-11-fluoro-8-(2-(2-methoxyethylamino)pyrimidin-4-yl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1'H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trione

HRID 245567노트

반응식

HRID 245567 반응식
[CH3:1][O:2][CH2:3][CH2:4][NH2:5].[F:6][C:7]1[C:8]2[O:33][N:32]=[C:31]([C:34]3[CH:39]=[CH:38][N:37]=[C:36](S(C)(=O)=O)[N:35]=3)[C:9]=2[CH:10]=[C:11]2[C:24]=1[N:23]1[CH2:25][C@@H:26]([CH3:30])[O:27][C@@H:28]([CH3:29])[C@@H:22]1[C:13]1([C:18](=[O:19])[NH:17][C:16](=[O:20])[NH:15][C:14]1=[O:21])[CH2:12]2.CS(C)=O.O(C(N)C)C>C1COCC1>[F:6][C:7]1[C:8]2[O:33][N:32]=[C:31]([C:34]3[CH:39]=[CH:38][N:37]=[C:36]([NH:5][CH2:4][CH2:3][O:2][CH3:1])[N:35]=3)[C:9]=2[CH:10]=[C:11]2[C:24]=1[N:23]1[CH2:25][C@@H:26]([CH3:30])[O:27][C@@H:28]([CH3:29])[C@@H:22]1[C:13]1([C:18](=[O:19])[NH:17][C:16](=[O:20])[NH:15][C:14]1=[O:21])[CH2:12]2

참가 물질

6

반응물 4

HCID 679Dimethyl SulfoxideHCID 80182-MethoxyethylamineHCID 19353429MethoxyethanamineHCID 67431840(2R,4S,4 aS)-11-fluoro-2,4-dimethyl-8-(2-(methylsulfonyl)pyrimidin-4-yl)-2,4,4a,6-tetrahydro-1H,1'H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trione

생성물 1

HCID 67433042(2R,4S,4aS)-11-fluoro-8-(2-(2-methoxyethylamino)pyrimidin-4-yl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1'H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trione수율 76.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

2-Methoxyethanamine (8.70 μL, 0.10 mmol) was added o a solution of (2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(2-(methylsulfonyl)pyrimidin-4-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3H)-trione (Example 169, 50 mg, 0.09 mmol) in THF (5 mL), and the mixture was stirred at room temperature for 3 hours, DMSO (1 ml) was added followed by the addition of 2 more equivalence of methoxylethanamine, the mixture was stirred at room temperature for over night. The crude was concentrated and purified by reverse phase silica gel column chromatography (20-70% MeCN in water gradient, 0.1% TFA) to give 37 mg of product.

후처리

  1. stirringthe mixture was stirred at room temperature for over night
  2. concentrationThe crude was concentrated
  3. custompurified by reverse phase silica gel column chromatography (20-70% MeCN in water gradient, 0.1% TFA)

출처 및 근거

ORD 기록
ord-2aaaae147b0c400a8fca3b08cd120347
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658641B2

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