Hydrazine hydrate (1:1) → HCID 123881419, compound

HRID 1509080Notes

Reaction equation

HRID 1509080 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)[C:24]([CH3:40])([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.[OH2:41].[NH2:42][NH2:43]>C(O)C>[C:9]([O:41][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:42][NH:43][C:36](=[O:37])[C:24]5([CH3:40])[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)2×HCID 67255412HCID 67255412, compound

Product 1

HCID 123881419HCID 123881419, compoundYield 45.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of methyl 2-(4-(1-((tert-butoxycarbonyl)amino)cyclobutyl)phenyl)-6-methyl-5-oxo-3-phenyl-5,6,7,8-tetrahydroquinoline-6-carboxylate (54 mg, 0.10 mmol) in anhydrous ethanol (1300 μL) was added hydrazine monohydrate (8 μL, 0.16 mmol). The reaction mixture was heated to reflux under a nitrogen atmosphere for 5 hours, additional hydrazine monohydrate (40 μL, 0.82 mmol) added, and the mixture heated at reflux for 18 hours. After cooling to room temperature the reaction mixture was concentrated to dryness under reduced pressure, purified by Biotage chromatography (silica, hexane:ethyl acetate, gradient elution from 88:12 to 0:100) to give the desired product as a yellow solid (12 mg, 23% yield). 1H-NMR (500 MHz, CDCl3) δ 8.72 (1H, s), 8.09 (1H, s), 7.34 (2H, d), 7.30 (2H, d), 7.23-7.28 (3H, m), 7.16-7.22 (2H, m), 5.05 (1H, br s), 3.32-3.44 (1H, m), 3.19-3.32 (1H, br m), 2.41-2.60 (4H, br m), 2.26-2.35 (1H, dd), 1.97-2.11 (2H, m), 1.74-1.86 (1H, m), 1.45 (3H, s), 1.14-1.44 (9H, br m). LCMS (Method A) RT=6.60 min, M+H+=523.17.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux under a nitrogen atmosphere for 5 hours
  3. temperaturethe mixture heated
  4. temperatureat reflux for 18 hours
  5. concentrationwas concentrated to dryness under reduced pressure
  6. custompurified by Biotage chromatography (silica, hexane:ethyl acetate, gradient elution from 88:12 to 0:100)

Sources & evidence

ORD record
ord-fd843f70c2914a8481cfcc4343cde633
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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