Hydrazine hydrate (1:1) → HCID 178452591, compound

HRID 1509077Notes

Reaction equation

HRID 1509077 reaction equation
C([O:5][C:6]([NH:8][C:9]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[C:28]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:27][C:26]4[C:25](=O)[CH:24]([C:36](OC)=[O:37])[CH2:23][CH2:22][C:21]=4[N:20]=3)=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)=O)(C)(C)C.[OH2:40].[NH2:41][NH2:42]>C(O)C>[C:9]([O:40][C:6](=[O:5])[NH:8][C:9]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[C:28]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[CH:27][C:26]4[C:25]5=[N:41][NH:42][C:36]([OH:37])=[C:24]5[CH2:23][CH2:22][C:21]=4[N:20]=3)=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)([CH3:13])([CH3:12])[CH3:10]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 67256387HCID 67256387, compound

Product 1

HCID 178452591HCID 178452591, compoundYield 67.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of methyl 2-(4-(1-((tert-butoxycarbonyl)amino)cyclobutyl)phenyl)-5-oxo-3-phenyl-5,6,7,8-tetrahydroquinoline-6-carboxylate (60 mg, 0.11 mmol) in anhydrous ethanol (1500 μL) was added hydrazine monohydrate (9 μL, 0.19 mmol). The reaction mixture was heated to reflux under a nitrogen atmosphere for 18 hours. After cooling to room temperature the reaction mixture was concentrated to dryness under reduced pressure, purified by Biotage chromatography (silica, dichloromethane:methanol, gradient elution from 99:1 to 90:10) and slurried in diethyl ether (1 mL) to give the desired product as a white solid (19 mg, 33% yield). 1H-NMR (500 MHz, CD3OD) δ 7.94 (1H, s), 7.32 (2H, d), 7.21-7.29 (5H, m), 7.14-7.21 (2H, m), 3.18 (2H, t), 2.81 (2H, t), 2.31-2.50 (4H, m), 2.00-2.12 (1, br m), 1.76-1.91 (1H, br m), 1.09-1.48 (br m). LCMS (Method A) RT=5.57 min, M+H+=509.17.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux under a nitrogen atmosphere for 18 hours
  3. concentrationwas concentrated to dryness under reduced pressure
  4. custompurified by Biotage chromatography (silica, dichloromethane:methanol, gradient elution from 99:1 to 90:10)

Sources & evidence

ORD record
ord-45cb3081309e40d18120883297c6a173
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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