Trifluoroacetic acid → (R)-1-methyl-9-(methyl(3-methylazetidin-3-yl)amino)-8-(trifluoromethyl)-3,5-dihydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-2(1H)-one trifluoroacetic acid

HRID 519061노트

반응식

HRID 519061 반응식
[CH3:1][C:2]1([N:13]([CH3:42])[C:14]2[C:15]([C:38]([F:41])([F:40])[F:39])=[CH:16][C:17]3[O:36][CH2:35][C:20]4=[N:21][N:22](COCC[Si](C)(C)C)[C:23](=[O:26])[CH:24]([CH3:25])[N:19]4[C:18]=3[CH:37]=2)[CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.[C:43]([OH:49])([C:45]([F:48])([F:47])[F:46])=[O:44]>C(Cl)Cl>[F:46][C:45]([F:48])([F:47])[C:43]([OH:49])=[O:44].[CH3:25][C@@H:24]1[C:23](=[O:26])[NH:22][N:21]=[C:20]2[CH2:35][O:36][C:17]3[CH:16]=[C:15]([C:38]([F:40])([F:39])[F:41])[C:14]([N:13]([CH3:42])[C:2]4([CH3:1])[CH2:3][NH:4][CH2:5]4)=[CH:37][C:18]=3[N:19]12

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 86727426Tert-butyl 3-methyl-3-(methyl(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(tri methylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate

생성물 1

HCID 86727427(R)-1-methyl-9-(methyl(3-methylazetidin-3-yl)amino)-8-(trifluoromethyl)-3,5-dihydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-2(1H)-one trifluoroacetic acid수율 7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of tert-butyl 3-methyl-3-(methyl(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(tri methylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate (0.586 g, 0.360 mmol) in DCM (4 mL) was added TFA (0.8 mL) and the mixture was stirred at ambient temperature for 1.5 h. The solvent was removed in vacuo and dioxane (1 mL) and ammonium hydroxide (25%, 1 mL) were added and the reaction mixture was stirred for 1.5 h at ambient temperature. The solvent was removed in vacuo and the residue was purified by HPLC (Table 3, Method 19) and further separated by chiral SFC (Table 2, Method 12) to give (R)-1-methyl-9-(methyl(3-methylazetidin-3-yl)amino)-8-(trifluoromethyl)-3,5-dihydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-2(1H)-one trifluoroacetic acid (SFC (Table 1, Method 17) Rt: 6.57 min, 0.033 g, 7%)) as a pale solid. LC/MS (Table 1, Method 5) Rt=2.319 min.; MS m/z: 384 [M+H]+.

후처리

  1. customThe solvent was removed in vacuo and dioxane (1 mL) and ammonium hydroxide (25%, 1 mL)
  2. additionwere added
  3. stirringthe reaction mixture was stirred for 1.5 h at ambient temperature
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by HPLC (Table 3, Method 19)
  6. customfurther separated by chiral SFC (Table 2, Method 12)

출처 및 근거

ORD 기록
ord-468a4a23a18d4b18941252ae123d4ee2
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115151B2

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