1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-{(1E)-3-[4-(2-Hydroxyethyl)piperidin-1-yl]-3-oxoprop-1-en-1-yl}-3,4-dihydro-1,8-naphthyridin-2(1H)-one

HRID 82911

Reaction equation

HRID 82911 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.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH:37]1[CH2:42][CH2:41][CH:40]([CH2:43][CH2:44][OH:45])[CH2:39][CH2:38]1.CCN=C=NCCCN(C)C>CN(C=O)C>[OH:45][CH2:44][CH2:43][CH:40]1[CH2:41][CH2:42][N:37]([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)[CH2:38][CH2:39]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 739534-PiperidineethanolHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66905305(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic Acid Hydrochloride

Product 1

HCID 529504366-{(1E)-3-[4-(2-Hydroxyethyl)piperidin-1-yl]-3-oxoprop-1-en-1-yl}-3,4-dihydro-1,8-naphthyridin-2(1H)-oneYield 55%

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), DMF (4.8 mL), HOBt (32 mg, 0.23 mmol), DIPEA (78 μL, 0.47 mmol), 4-piperidineethanol (30 mg, 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 on column chromatography (eluent: dichloromethane/MeOH, 95/5) to give a white solid. This solid was triturated in MeOH, filtered, washed with MeOH and diethyl ether and dried to give the title compound (35 mg, 55%) as a white solid.

Workup

  1. concentrationconcentrated to dryness
  2. customThe residue was purified on column chromatography (eluent: dichloromethane/MeOH, 95/5)
  3. customto give a white solid
  4. customThis solid was triturated in MeOH
  5. filtrationfiltered
  6. washwashed with MeOH and diethyl ether
  7. customdried

Sources & evidence

ORD record
ord-e0e86a585d484ec2be7fcff466e2ef76
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Linked notes

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