1,2-Dichloroethane → 3-{[1-Benzyl-3-(2-dimethylamino-pyrimidin-5-yl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid methyl ester

HRID 919925Notes

Reaction equation

HRID 919925 reaction equation
CO[C:3]([C:5]1[C:6]([OH:32])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:23]1[CH:24]=[N:25][C:26]([N:29]([CH3:31])[CH3:30])=[N:27][CH:28]=1)=[CH:8]2)=[O:4].[OH-].[Na+].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[CH3:50][O:51][C:52](=[O:56])[CH2:53][CH2:54][NH2:55].CCN(C(C)C)C(C)C>CO.C1COCC1>[CH3:50][O:51][C:52](=[O:56])[CH2:53][CH2:54][NH:55][C:3]([C:5]1[C:6]([OH:32])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[N:27][C:26]([N:29]([CH3:31])[CH3:30])=[N:25][CH:24]=1)=[CH:8]2)=[O:4]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 682974441-Benzyl-3-(2-dimethylamino-pyrimidin-5-yl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 682975973-{[1-Benzyl-3-(2-dimethylamino-pyrimidin-5-yl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid methyl esterYield 85.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-benzyl-3-(2-dimethylamino-pyrimidin-5-yl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (30 mg, 0.07 mmol), 2 M NaOH (4 mL, THF (4 mL) and MeOH (4 mL) was stirred at r.t. for 16 h. The resulting mixture was concentrated to dryness, and diluted with water (5 mL). 1 M HCl was added until pH was about 4, and the resulting precipitate was isolated by filtration and dried under high vacuum. The crude solid was dissolved in CH2Cl2, and HOBt (12 mg, 0.09 mmol) and EDC (23 mg, 0.12 mmol) were added. The resulting mixture was stirred for 10 min. β-Alanine methyl ester HCl salt (13 mg, 0.09 mmol) and Hunig's base (0.030 mL, 0.21 mmol) were then added, and the mixture was stirred for 20 h. The solvent was evaporated in vacuo, and the residue was purified by silica gel chromatography (5-80% EtOAc/hexanes+1% AcOH) to give 30 mg of the title compound as a pale yellow solid. MS: (+) m/z 503.33 (M+1).

Workup

  1. concentrationThe resulting mixture was concentrated to dryness
  2. additiondiluted with water (5 mL)
  3. addition1 M HCl was added until pH was about 4
  4. customthe resulting precipitate was isolated by filtration
  5. customdried under high vacuum
  6. dissolutionThe crude solid was dissolved in CH2Cl2
  7. additionwere then added
  8. stirringthe mixture was stirred for 20 h
  9. customThe solvent was evaporated in vacuo
  10. customthe residue was purified by silica gel chromatography (5-80% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-ad152a56fd9e4934a52ff577164e7fb9
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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