1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-[(1E)-3-Oxo-3-(3-phenoxyazetidin-1-yl)prop-1-en-1-yl]-3,4-dihydro-1,8-naphthyridin-2(1H)-one

HRID 633873Notes

Reaction equation

HRID 633873 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.Cl.[O:19]([CH:26]1[CH2:29][NH:28][CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[O:17]=[C:15]([N:28]1[CH2:27][CH:26]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:29]1)/[CH:14]=[CH:13]/[C:8]1[CH:7]=[C:6]2[C:11](=[N:10][CH:9]=1)[NH:12][C:3](=[O:2])[CH2:4][CH2:5]2

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 185264463-Phenoxyazetidine hydrochlorideHCID 66905305(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic Acid Hydrochloride

Product 1

HCID 529504386-[(1E)-3-Oxo-3-(3-phenoxyazetidin-1-yl)prop-1-en-1-yl]-3,4-dihydro-1,8-naphthyridin-2(1H)-oneYield 36%

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 (30 mg, 0.12 mmol), DMF (3 mL), 3-phenoxyazetidine hydrochloride (26 mg, 0.14 mmol; which may be prepared as described in Step 3), DIPEA (48 μL, 0.28 mmol) and EDAC (27 mg, 0.14 mmol). The reaction mixture was stirred at room temperature overnight and concentrated to dryness. The residue was purified on preparative TLC (eluent: dichloromethane/NH3 7N in MeOH, 2.5%) to give a pale yellow solid. This solid was triturated in acetone, filtered, washed with acetone and diethyl ether then dried to give the title compound (15 mg, 36%) as a white solid.

Workup

  1. concentrationconcentrated to dryness
  2. customThe residue was purified on preparative TLC (eluent: dichloromethane/NH3 7N in MeOH, 2.5%)
  3. customto give a pale yellow solid
  4. customThis solid was triturated in acetone
  5. filtrationfiltered
  6. washwashed with acetone and diethyl ether
  7. customthen dried

Sources & evidence

ORD record
ord-c95cd831ccbe4882846b0084cfb10461
Source dataset
uspto-grants-2016_04
Patent number
US09321769B2

Reaction notes

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