Azetidine → 6-[(1E)-3-Azetidin-1-yl-3-oxoprop-1-en-1-yl]-3,4-dihydro-1,8-naphthyridin-2(1H)-one

HRID 82908Notes

Reaction equation

HRID 82908 reaction equation
Cl.[O:2]=[C:3]1[NH:12][C:11]2[N:10]=[CH:9][C:8](/[CH:13]=[CH:14]/[C:15]([OH:17])=O)=[CH:7][C:6]=2[CH2:5][CH2:4]1.BrC1C=[C:21]2[C:26](=[N:27][CH:28]=1)NC(=O)CC2.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.N1CCC1.CCN=C=NCCCN(C)C>CN(C=O)C>[N:27]1([C:15](=[O:17])/[CH:14]=[CH:13]/[C:8]2[CH:7]=[C:6]3[C:11](=[N:10][CH:9]=2)[NH:12][C:3](=[O:2])[CH2:4][CH2:5]3)[CH2:26][CH2:21][CH2:28]1

Participants

8

Reactant 6

HCID 10422AzetidineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 110963256-Bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-oneHCID 66905305(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic Acid Hydrochloride

Product 1

HCID 683381416-[(1E)-3-Azetidin-1-yl-3-oxoprop-1-en-1-yl]-3,4-dihydro-1,8-naphthyridin-2(1H)-oneYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 16 mL vial flask was successively charged with (2E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic acid hydrochloride (50 mg, 0.20 mmol), prepared (as in J. Med. Chem. 2003, 46, 9, 1627-1635) from 6-bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-one described in U.S. Pat. No. 4,866,074 (Rorer Pharmaceutical Corp.), DMF (4.8 mL), HOBt (32 mg, 0.23 mmol), DIPEA (78 μL, 0.47 mmol), azetidine (16 μL, 0.23 mmol) and EDAC (45 mg, 0.23 mmol). The reaction mixture was stirred at room temperature overnight and concentrated to dryness. The residue was purified twice on preparative TLC (eluent: dichloromethane/MeOH, 95/5) to give the title compound (31 mg, 62%) as a white solid.

Workup

  1. concentrationconcentrated to dryness
  2. customThe residue was purified twice on preparative TLC (eluent: dichloromethane/MeOH, 95/5)

Sources & evidence

ORD record
ord-552823ab151248efbd947804d53dcc00
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Reaction notes

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