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 1468076ノート

反応式

HRID 1468076 の反応式
[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

参加物

8

反応物 4

HCID 3776IsopropanolHCID 9005Trimethyl orthoformateHCID 207652372-Oxopropanethioamide2 回HCID 867067236'-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-imine

生成物 1

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

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 8857Ethyl Acetate溶媒HCID 8900Heptane溶媒

反応条件

温度
60 °C

実験手順

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]+.

後処理

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

出典と根拠

ORDレコード
ord-abbc71761ad84c3f854d55136a54d790
出典データセット
uspto-grants-2015_04
特許番号
US09000185B2

反応ノート

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