Isopropanol → 6'-[(3,3-Difluorocyclobutyl)methoxy]-4-methoxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazole]-4''(3''H)-thione

HRID 1468076노트

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HRID 1468076 반응식
[F:1][C:2]1([F:25])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][C:13]4([CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]4)[C:14]3=[NH:17])=[CH:10][CH:9]=2)[CH2:3]1.C(OC)(OC)OC.CC(O)C.O=[C:38]([CH3:42])[C:39](=[S:41])[NH2:40]>CO.CCCCCCC.CCOC(C)=O>[F:1][C:2]1([F:25])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][C:13]4([C:14]53[NH:40][C:39](=[S:41])[C:38]([CH3:42])=[N:17]5)[CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]4)=[CH:10][CH:9]=2)[CH2:3]1

참가 물질

8

반응물 4

HCID 3776IsopropanolHCID 9005Trimethyl orthoformateHCID 207652372-Oxopropanethioamide2회HCID 867067236'-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-imine

생성물 1

HCID 867067246'-[(3,3-Difluorocyclobutyl)methoxy]-4-methoxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazole]-4''(3''H)-thione수율 12%

시약·촉매·용매 3

HCID 887Methanol용매HCID 8857Ethyl Acetate용매HCID 8900Heptane용매

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온도
60 °C

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. concentrationThe mixture was concentrated in vacuo
  2. customThe product was isolated

출처 및 근거

ORD 기록
ord-abbc71761ad84c3f854d55136a54d790
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09000185B2

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