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

HRID 920035Notes

Reaction equation

HRID 920035 reaction equation
C[O:2][C:3]([C:5]1[C:6]([OH:34])=[C:7]2[C:12](=[C:13]([C:15]3[S:16][CH:17]=[CH:18][N: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.[OH-].[Na+].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[CH3:52][O:53][C:54](=[O:58])[CH2:55][CH2:56][NH2:57].CCN(C(C)C)C(C)C>C(Cl)Cl.C1COCC1.CO>[CH3:52][O:53][C:54](=[O:58])[CH2:55][CH2:56][NH:57][C:3]([C:5]1[C:6]([OH:34])=[C:7]2[C:12](=[C:13]([C:15]3[S:16][CH:17]=[CH:18][N: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:2]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 1363772481-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-thiazol-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 1363772493-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-thiazol-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid methyl esterYield 37%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-thiazol-2-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 then acidified to pH about 3 with 1 M HCl. The resulting suspension was 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. β-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. The mixture was concentrated in vacuo, and the residue was purified by silica gel chromatography (5-40% EtOAc/hexanes+1% AcOH) to give 28 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. 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 16 h
  7. concentrationThe mixture was concentrated in vacuo
  8. customthe residue was purified by silica gel chromatography (5-40% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-a2438e897586410e9a5cfb62923c2cf2
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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