Hydrazinecarboxylic acid, ethyl ester → Tert-butyl(1-(4-(3-oxo-9-phenyl-2,3,5,6-tetrahydro-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-8-yl)phenyl)cyclobutyl)carbamate

HRID 1509112Notes

Reaction equation

HRID 1509112 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:26][C:25]4[C:24](=S)[NH:23][CH2:22][CH2:21][C:20]=4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:36](OCC)(=[O:39])[NH:37][NH2:38]>C1COCC1.C([O-])(=O)C.[Hg+]>[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:26][C:25]4[C:24]5=[N:38][NH:37][C:36](=[O:39])[N:23]5[CH2:22][CH2:21][C:20]=4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 20064Hydrazinecarboxylic acid, ethyl esterHCID 123633046Tert-butyl(1-(4-(3-phenyl-5-thioxo-5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)phenyl)cyclobutyl)carbamate

Product 1

HCID 123922000Tert-butyl(1-(4-(3-oxo-9-phenyl-2,3,5,6-tetrahydro-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-8-yl)phenyl)cyclobutyl)carbamateYield 56%

Reagents, catalysts & solvents 2

HCID 61181Mercurous acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl(1-(4-(3-phenyl-5-thioxo-5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)phenyl)cyclobutyl)carbamate (55 mg, 0.113 mmol) in THF (7 mL) was added ethyl carbazate (23.6 mg, 0.226 mmol) and mercury acetate (54.1 mg, 0.17 mmol) under nitrogen. The resulting mixture was stirred at r.t. for 2 h. The mixture was concentrated to dryness under reduced pressure and partitioned between DCM (15 ml) and water (15 ml). The organic phase was separated and concentrated to dryness under reduced pressure. The resulting residue was suspended in toluene (7 ml). The resulting mixture was heated under reflux for 3 h. After cooled down to room temperature, the mixture was concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 4% MeOH in dichloromethane) to give tert-butyl(1-(4-(3-oxo-9-phenyl-2,3,5,6-tetrahydro-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-8-yl)phenyl)cyclobutyl)carbamate (32 mg, 56%). LCMS (Method A): RT=6.29 min, M+1=510. 1H NMR (500 MHz, CDCl3): 9.83 (1H,S), 8.10 (1H, s), 7.29 (2H, d), 7.22 (2H, d), 7.19-7.18 (3H, m), 7.13-7.11 (2H, m), 5.1 (1H, br), 4.01 (2H, t), 3.36 (2H, t), 2.43-2.28 (4H, m), 2.02-1.97 (1H, m), 1.76-1.70 (1H, m), 1.30-1.14 (9H, br).

Workup

  1. concentrationThe mixture was concentrated to dryness under reduced pressure
  2. custompartitioned between DCM (15 ml) and water (15 ml)
  3. customThe organic phase was separated
  4. concentrationconcentrated to dryness under reduced pressure
  5. temperatureThe resulting mixture was heated
  6. temperatureunder reflux for 3 h
  7. temperatureAfter cooled down to room temperature
  8. concentrationthe mixture was concentrated to dryness under reduced pressure
  9. customThe resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 4% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-92b978addba048c4b68aa951eeeaffe2
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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