1,2-Dichloroethane → HCID 136377246, compound

HRID 1411029Notes

Reaction equation

HRID 1411029 reaction equation
CO[C:3]([C:5]1[C:6]([OH:35])=[C:7]2[C:12](=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[N:14]=1)[N:11]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:10](=[O:28])[C:9]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[CH:8]2)=[O:4].[OH-].[Na+].C1C=CC2N(O)N=[N:44][C:42]=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.C[CH2:62][O:63][C:64]([CH3:66])=[O:65]>O.C(Cl)Cl.C1COCC1.CO>[CH3:62][O:63][C:64](=[O:65])[CH2:66][CH2:42][NH:44][C:3]([C:5]1[C:6]([OH:35])=[C:7]2[C:12](=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[N:14]=1)[N:11]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:10](=[O:28])[C:9]([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[CH:8]2)=[O:4]

Participants

11

Reactant 6

HCID 111,2-DichloroethaneHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 136377245HCID 136377245, compound

Product 1

HCID 136377246HCID 136377246, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carb oxylic acid methyl ester (80 mg, 0.17 mmol), 2 M NaOH (3 mL), MeOH (3 mL) and THF (3 mL) was stirred at r.t. for 16 h. The mixture was concentrated to approximately one-third of its original volume, and then acidified to pH about 3-4. The resulting suspension was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated. To the residue were then added HOBt (37 mg, 0.28 mmol), CH2Cl2 (3 mL), and EDC (60 mg, 0.31 mmol), and the resulting mixture was stirred for 10 min. (3-Alanine methyl ester HCl salt (39 mg, 0.28 mmol) and Hunig's base (0.11 mL, 0.62 mmol) were added, and the mixture was stirred for 48 h. The mixture was diluted with EtOAc and water, and acidified to pH about 3-4. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-70% EtOAc/hexanes+1% AcOH) to give 62 mg of the title compound. MS: (+) m/z 535.58 (M+1).

Workup

  1. concentrationThe mixture was concentrated to approximately one-third of its original volume
  2. extractionThe resulting suspension was extracted with EtOAc
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. additionwere added
  6. stirringthe mixture was stirred for 48 h
  7. dry with materialThe organic layer was dried over MgSO4
  8. concentrationconcentrated
  9. customThe crude product was purified by silica gel chromatography (5-70% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-2209309aee6d4429bf92acf4014b42ea
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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