Sodium Carbonate → 6-[3-(3-Acetyl-azetidin-1-yl)-3-oxo-propenyl]-3,4-dihydro-1H-[1,8]naphthyridin-2-one

HRID 634008ノート

反応式

HRID 634008 の反応式
OC(C(F)(F)F)=O.[NH:8]1[CH2:11][CH:10]([C:12](=[O:14])[CH3:13])[CH2:9]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.[O:46]=[C:47]1[NH:56][C:55]2[N:54]=[CH:53][C:52](/[CH:57]=[CH:58]/[C:59](O)=[O:60])=[CH:51][C:50]=2[CH2:49][CH2:48]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.O.C(OCC)(=O)C>[C:12]([CH:10]1[CH2:11][N:8]([C:59](=[O:60])[CH:58]=[CH:57][C:52]2[CH:51]=[C:50]3[C:55](=[N:54][CH:53]=2)[NH:56][C:47](=[O:46])[CH2:48][CH2:49]3)[CH2:9]1)(=[O:14])[CH3:13]

参加物

10

反応物 6

HCID 10340Sodium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66905305(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic Acid HydrochlorideHCID 866729861-(Azetidin-3-yl)ethan-1-one; trifluoroacetic acid

生成物 1

HCID 671546786-[3-(3-Acetyl-azetidin-1-yl)-3-oxo-propenyl]-3,4-dihydro-1H-[1,8]naphthyridin-2-one収率 50.1%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

1-Azetidin-3-yl-ethanone TFA (700 mg, 3.54 mmol), EDCI (676 mg, 3.54 mmol), HOBt (477 mg, 3.54 mmol) and diisopropylethylamine (2.1 mL, 11.8 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (600 mg, 2.36 mmol) in dimethylformamide (15 mL) at room temperature. The reaction mixture was stirred overnight. The reaction mixture was then diluted by addition of ethyl acetate (40 mL) and water (40 mL). The organic layer was discarded and the aqueous layer was basified with an aqueous solution of saturated sodium carbonate until pH=12 and finally extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×50 mL), dried over sodium sulfate and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (1:0 to 95:5) as eluent to obtain the title compound as a white solid (354 mg, 50%).

後処理

  1. extractionfinally extracted with ethyl acetate (2×50 mL)
  2. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×50 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to dryness
  5. customThe residue was purified by chromatography on silica gel

出典と根拠

ORDレコード
ord-192accc309d244059c7e4e97445d0c36
出典データセット
uspto-grants-2016_04
特許番号
US09321769B2

反応ノート

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