Hydrochloric Acid → 6'-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-imine

HRID 1468075노트

반응식

HRID 1468075 반응식
Cl.[F:2][C:3]1([F:32])[CH2:6][CH:5]([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[CH2:14][C:13]2([CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]2)[C:12]3=[N:25]S(C(C)(C)C)=O)[CH2:4]1>O1CCOCC1.C([O-])(O)=O.[Na+]>[F:2][C:3]1([F:32])[CH2:6][CH:5]([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15]([CH2:14][C:13]4([CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]4)[C:12]3=[NH:25])=[CH:16][CH:17]=2)[CH2:4]1

참가 물질

5

반응물 2

HCID 313Hydrochloric AcidHCID 86706722N-(5'-((3,3-Difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide2회

생성물 1

HCID 867067236'-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-imine수율 116.4%

시약·촉매·용매 2

HCID 312751,4-Dioxane용매HCID 516892Sodium Bicarbonate용매

실험 절차

HCl (4 M in 1,4-dioxane, 4.13 mL, 16.5 mmol) was added to a solution of N-(5′-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2′-indene]-3′(1′H)-ylidene)-2-methylpropane-2-sulfinamide (Intermediate 18, 750 mg, 1.65 mmol) in anhydrous 1,4-dioxane (25 mL). A white precipitate formed immediately and the resulting cloudy mixture was stirred under a nitrogen atmosphere overnight. The mixture was diluted with NaHCO3 (aq.) and extracted with DCM. The organic phase was dried and concentrated, to yield 6′-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-imine (672 mg, 1.92 mmol). The imine, trimethyl orthoformate (0.557 mL, 5.08 mmol) and 2-propanol (5 mL) was placed into a MW tube and the mixture was heated at 60° C. in an oil bath. 2-oxopropanethioamide (Intermediate 1, 397 mg, 3.85 mmol) in MeOH (15 mL) was added and the resulting mixture was stirred overnight. The mixture was concentrated in vacuo. The product was isolated using column chromatography (0-50% EtOAc in heptane) to give 106 mg (12% yield) of the title compound. MS (ES+) m/z 435 [M+H]+.

후처리

  1. customA white precipitate formed immediately
  2. extractionextracted with DCM
  3. customThe organic phase was dried
  4. concentrationconcentrated

출처 및 근거

ORD 기록
ord-55b30e1edd3d48d58326e4253076e6de
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09000185B2

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