1,2-Dichloroethane → HCID 68297645, compound

HRID 1411046Notes

Reaction equation

HRID 1411046 reaction equation
CO[C:3]([C:5]1[C:6]([OH:34])=[C:7]2[C:12](=[C:13]([C:15]3[N:16]=[CH:17][S:18][CH:19]=3)[N:14]=1)[N:11]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:10](=[O:27])[C:9]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[CH:8]2)=[O:4].[OH-].[Na+].C1C=CC2N(O)N=[N:43][C:41]=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.C[CH2:61][O:62][C:63]([CH3:65])=[O:64]>C(Cl)Cl.C1COCC1.CO>[CH3:61][O:62][C:63](=[O:64])[CH2:65][CH2:41][NH:43][C:3]([C:5]1[C:6]([OH:34])=[C:7]2[C:12](=[C:13]([C:15]3[N:16]=[CH:17][S:18][CH:19]=3)[N:14]=1)[N:11]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:10](=[O:27])[C:9]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)=[CH:8]2)=[O:4]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 682976071-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-thiazol-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 68297645HCID 68297645, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-thiazol-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (64 mg, 0.14 mmol), 2 M NaOH (3 mL), MeOH (3 mL) and THF (3 mL) was stirred at r.t. overnight. The mixture was concentrated to approximately one-third of its original volume, and the resulting mixture was acidified to pH about 3-4 and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated. To the residue were then added HOBt (30 mg, 0.22 mmol), CH2Cl2 (3 mL), and EDC (47 mg, 0.25 mmol), and the resulting mixture was stirred for 10 min. (3-Alanine methyl ester HCl salt (31 mg, 0.22 mmol) and Hunig's base (0.1 mL, 0.49 mmol) were added, and the mixture was stirred for 16 h. EtOAc (30 mL) was added, and the mixture was washed with 0.1 M HCl. The organic layer was dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (5-70% EtOAc/hexanes+1% AcOH) to give 24 mg of the title compound. MS: (+) m/z 541.31 (M+1).

Workup

  1. concentrationThe mixture was concentrated to approximately one-third of its original volume
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. additionwere added
  6. stirringthe mixture was stirred for 16 h
  7. washthe mixture was washed with 0.1 M HCl
  8. dry with materialThe organic layer was dried over MgSO4
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography (5-70% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-7358f292b1e74b28a2bef635ad810380
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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