1,2-Dichloroethane → 3-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-2,2-dimethyl-propionic acid ethyl ester

HRID 1411024Notes

Reaction equation

HRID 1411024 reaction equation
[CH2:1]([N:8]1[C:17]2[C:12](=[C:13]([OH:27])[C:14]([C:24]([OH:26])=O)=[N:15][C:16]=2[C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[CH:11]=[C:10]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:9]1=[O:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[CH2:50]([O:52][C:53](=[O:59])[C:54]([CH3:58])([CH3:57])[CH2:55][NH2:56])[CH3:51].CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O.[Cl-].[Na+].O.Cl>[CH2:50]([O:52][C:53](=[O:59])[C:54]([CH3:58])([CH3:57])[CH2:55][NH:56][C:24]([C:14]1[C:13]([OH:27])=[C:12]2[C:17](=[C:16]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:15]=1)[N:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:9](=[O:34])[C:10]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)=[CH:11]2)=[O:26])[CH3:51]

Participants

10

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 18698433Ethyl 3-amino-2,2-dimethylpropanoate hydrochlorideHCID 682974401-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid

Product 1

HCID 682974583-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-2,2-dimethyl-propionic acid ethyl esterYield 44.1%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid (53 mg, 0.118 mmol) and HOBt (26 mg, 0.189 mmol) was dissolved in CH2Cl2 (3 mL). EDC (41 mg, 0.212 mmol) was added, and the resulting mixture was stirred for 10 min. 3-Amino-2,2-dimethyl-propionic acid ethyl ester HCl salt (34 mg, 0.189 mmol) and Hunig's base (0.075 mL, 0.425 mmol) were added, and the mixture was stirred overnight. The mixture was diluted with EtOAc and brine, and 1 M HCl was added until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-60% EtOAc/hexanes+1% AcOH) to give 30 mg of the title compound. MS: (+) m/z 577.40 (M+1).

Workup

  1. stirringthe mixture was stirred overnight
  2. additionwas added until pH was about 3-4
  3. extractionThe aqueous layer was extracted with additional EtOAc
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel chromatography (5-60% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-2405fa45537f4c90a5588cf2ddb00120
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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