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

HRID 2172010Notes

Reaction equation

HRID 2172010 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.[NH:19]1[CH2:22][CH:21]([O:23][CH2:24][C:25]2[S:26][CH:27]=[CH:28][N:29]=2)[CH2:20]1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C>[O:17]=[C:15]([N:19]1[CH2:22][CH:21]([O:23][CH2:24][C:25]2[S:26][CH:27]=[CH:28][N:29]=2)[CH2:20]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

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 66905305(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic Acid HydrochlorideHCID 671544802-[(Azetidin-3-yloxy)methyl]-1,3-thiazole hydrochloride

Product 1

HCID 529505266-{(1E)-3-Oxo-3-[3-(1,3-thiazol-2-ylmethoxy)azetidin-1-yl]prop-1-en-1-yl}-3,4-dihydro-1,8-naphthyridin-2(1H)-oneYield 24%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 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 (60 mg, 0.24 mmol), DMF (5.8 mL), 2-[(azetidin-3-yloxy)methyl]-1,3-thiazole hydrochloride (99 mg, 0.48 mmol; which may be prepared as described in Step 3), DIPEA (119 μL, 0.72 mmol), DMAP (2.4 mg, 0.02 mmol) and EDAC (56 mg, 0.29 mmol). The reaction mixture was stirred at room temperature overnight and concentrated to dryness. The residue was precipitated in methanol/water and then filtered. The resulting solid was purified on column chromatography (eluent: 96/4 dichloromethane/MeOH) then triturated in pentane and MeOH to give the title compound (21 mg, 24%) as a white solid.

Workup

  1. concentrationconcentrated to dryness
  2. customThe residue was precipitated in methanol/water
  3. filtrationfiltered
  4. customThe resulting solid was purified on column chromatography (eluent: 96/4 dichloromethane/MeOH)
  5. customthen triturated in pentane

Sources & evidence

ORD record
ord-97e3a19b3c3847ad86046db7b3f50d78
Source dataset
uspto-grants-2015_06
Patent number
US09051321B2

Reaction notes

Loading…