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6-chloro-3-(2-ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxy-N,N-dimethylbenzamide → 6-chloro-2-hydroxy-N,N-dimethyl-3-(2-{[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}-3,4-dioxocyclobut-1-enylamino)benzamide

HRID 1528217
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HRID 1528217 반응식
[CH3:1][C:2]1[O:6][C:5]([C@H:7]([NH2:13])[C:8]2([CH3:12])[CH2:11][O:10][CH2:9]2)=[CH:4][CH:3]=1.[Cl:14][C:15]1[C:20]([C:21]([N:23]([CH3:25])[CH3:24])=[O:22])=[C:19]([OH:26])[C:18]([NH:27][C:28]2[C:31](=O)[C:30](=[O:33])[C:29]=2[O:34]CC)=[CH:17][CH:16]=1>CO>[Cl:14][C:15]1[C:20]([C:21]([N:23]([CH3:25])[CH3:24])=[O:22])=[C:19]([OH:26])[C:18]([NH:27][C:28]2[C:29](=[O:34])[C:30](=[O:33])[C:31]=2[NH:13][C@@H:7]([C:5]2[O:6][C:2]([CH3:1])=[CH:3][CH:4]=2)[C:8]2([CH3:12])[CH2:9][O:10][CH2:11]2)=[CH:17][CH:16]=1
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참가 물질

4

반응물 2

HCID 895255256-chloro-3-(2-ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxy-N,N-dimethylbenzamideHCID 89525580C-(R)-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine

생성물 1

HCID 715259756-chloro-2-hydroxy-N,N-dimethyl-3-(2-{[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}-3,4-dioxocyclobut-1-enylamino)benzamide수율 53%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A mixture of 412 mg (2.27 mmol, 1.1 eq) of C—(R)-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine (prepared in EXAMPLE 50, steps 1 to 4) and 700 mg (2.07 mmol, 1 eq) of 6-chloro-3-(2-ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxy-N,N-dimethylbenzamide in 45 ml of methanol was stirred at ambient temperature for 3 days. The methanol was evaporated off and the residue was taken up with ethyl acetate and washed with a 1 M aqueous sodium dihydrogen phosphate solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. The residue (0.90 g) was chromatographed on silica gel (80 g prepacked column, eluent dichloromethane/methanol, from 0 to 10% of methanol). 520 mg of 6-chloro-2-hydroxy-N,N-dimethyl-3-(2-{[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}-3,4-dioxocyclobut-1-enylamino)benzamide were obtained in the form of an ochre solid. Yield=53%. Mp=165-167° C.

후처리

  1. customThe methanol was evaporated off
  2. washwashed with a 1 M aqueous sodium dihydrogen phosphate solution
  3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue (0.90 g) was chromatographed on silica gel (80 g prepacked column, eluent dichloromethane/methanol, from 0 to 10% of methanol)

출처 및 근거

ORD 기록
ord-9de151fb976e4d98a7b2f3307e71b6df
출처 데이터셋
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09090596B2

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