1,2-Dichloroethane → 1-benzyl-4-(benzyloxy)-N-{4-fluoro-2-[(methylamino)carbonyl]benzyl}-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide

HRID 1179327Notes

Reaction equation

HRID 1179327 reaction equation
[CH2:1]([N:8]1[C:17]2[C:12](=[N:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:10]([C:26]([OH:28])=O)[C:9]1=[O:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.[Cl-].[F:45][C:46]1[CH:51]=[CH:50][C:49]([CH2:52][NH3+:53])=[C:48]([C:54]([NH:56][CH3:57])=[O:55])[CH:47]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:1]([N:8]1[C:17]2[C:12](=[N:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[C:10]([C:26]([NH:53][CH2:52][C:49]2[CH:50]=[CH:51][C:46]([F:45])=[CH:47][C:48]=2[C:54]([NH:56][CH3:57])=[O:55])=[O:28])[C:9]1=[O:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 111,2-Dichloroethane2×HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 589780031-Benzyl-4-(benzyloxy)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylic acidHCID 866001764-Fluoro-2-[(methylamino)carbonyl]benzylamine hydrochloride

Product 1

HCID 589779971-benzyl-4-(benzyloxy)-N-{4-fluoro-2-[(methylamino)carbonyl]benzyl}-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-benzyl-4-(benzyloxy)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylic acid (0.15 g, 0.39 mmol) in DMF (4 mL) was added HOAT (0.26 g, 1.94 mmol) and EDC (0.07 g, 0.47 mmol). The solution was stirred for 10 minutes at which time EDC (0.036 g, 0.23 mmol), {4-fluoro-2-[(methylamino)carbonyl]phenyl}methanaminium chloride (0.108 g, 0.47 mmol), and DIEA (0.10 g, 0.78 mmol) were added. The reaction was then stirred at room temperature overnight at which time the solution was purified by preparative reverse phase HPLC eluting with a gradient of 5-95% acetonitrile/water (0.1% TFA). The fractions that contained the desired product were concentrated. Note that during the prep des-O-benzyl product was also obtained. The mixture was taken on to the next step.

Workup

  1. additionwere added
  2. customwas purified by preparative reverse phase HPLC
  3. washeluting with a gradient of 5-95% acetonitrile/water (0.1% TFA)
  4. concentrationwere concentrated
  5. customwas also obtained

Sources & evidence

ORD record
ord-851879903ded4fe497ddd7f4017124e8
Source dataset
uspto-grants-2007_10
Patent number
US07279487B2

Reaction notes

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