1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-6-(3-(3-acetylazetidin-1-yl)-3-oxoprop-1-enyl)-1'-methyl-1H-spiro[[1,8]naphthyridine-3,4'-piperidin]-2(4H)-one

HRID 83078Notes

Reaction equation

HRID 83078 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([C:6](=[O:8])[CH3:7])[CH2:3]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.[CH3:40][N:41]1[CH2:46][CH2:45][C:44]2([CH2:55][C:54]3[C:49](=[N:50][CH:51]=[C:52](/[CH:56]=[CH:57]/[C:58](O)=[O:59])[CH:53]=3)[NH:48][C:47]2=[O:61])[CH2:43][CH2:42]1>CN(C)C=O>[C:6]([CH:4]1[CH2:5][N:2]([C:58](=[O:59])/[CH:57]=[CH:56]/[C:52]2[CH:53]=[C:54]3[C:49](=[N:50][CH:51]=2)[NH:48][C:47](=[O:61])[C:44]2([CH2:45][CH2:46][N:41]([CH3:40])[CH2:42][CH2:43]2)[CH2:55]3)[CH2:3]1)(=[O:8])[CH3:7]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67154626HCID 67154626, compoundHCID 67154659HCID 67154659, compound

Product 1

HCID 68338069(E)-6-(3-(3-acetylazetidin-1-yl)-3-oxoprop-1-enyl)-1'-methyl-1H-spiro[[1,8]naphthyridine-3,4'-piperidin]-2(4H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(Azetidin-3-yl)ethanone hydrochloride (110 mg, 0.8 mmol), EDCI (153 mg, 0.8 mmol), HOBt (108 mg, 0.8 mmol) and diisopropylethylamine (700 μL, 4.0 mmol) were successively added to a solution of (E)-3-(1′-methyl-2-oxo-2,4-dihydro-1H-spiro[[1,8]naphthyridine-3,4′-piperidine]-6-yl)acrylic acid hydrochloride (136 mg, 0.4 mmol) in dimethylformamide (15 mL) at room temperature. The reaction mixture was stirred overnight. After concentration to dryness, the residue was purified by chromatography on silica gel using dichloromethane/methanol/ammoniac (9:1:0.1) as eluent. Precipitation in a mixture DCM/pentane allowed isolation of the title product as a yellow solid (44.6 mg, 29%).

Workup

  1. concentrationAfter concentration to dryness
  2. customthe residue was purified by chromatography on silica gel
  3. customPrecipitation in a mixture DCM/pentane allowed isolation of the title product as a yellow solid (44.6 mg, 29%)

Sources & evidence

ORD record
ord-c6380f37b18c4075aa6a23b497942a03
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Reaction notes

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