Methylamine → HCID 178482482, compound

HRID 1509085Notes

Reaction equation

HRID 1509085 reaction equation
[C:1]([O:5][C:6](=[O:40])[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](=O)[C:23](=[C:35](SC)SC)[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].[CH3:41][NH2:42].O.[NH2:44][NH2:45]>C(O)C>[C:1]([O:5][C:6](=[O:40])[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:44][NH:45][C:35]([NH:42][CH3:41])=[C:23]5[CH2:22][CH2:21][C:20]=4[N:19]=3)=[CH:14][CH:13]=2)[CH2:9][CH2:10][CH2:11]1)([CH3:2])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 6329Methylamine2×HCID 24654Hydrazine hydrate (1:1)HCID 123658741HCID 123658741, compound

Product 1

HCID 178482482HCID 178482482, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl(1-(4-(6-(bis(methylthio)methylene)-5-oxo-3-phenyl-5,6,7,8-tetrahydroquinolin-2-yl)phenyl)cyclobutyl)carbamate (100 mg, 0.18 mmol) in ethanol (873 μl) was added methylamine (2M in THF, 87 μl, 0.18 mmol) and the mixture heated to 80° C. under a nitrogen atmosphere for 2 hours. Further methylamine (2M in THF, 873 μl, 1.746 mmol) was added and the mixture heated to 80° C. under a nitrogen atmosphere for 2 hours. Hydrazine monohydrate (25.4 μl, 0.52 mmol) was added and the mixture heated to 80° C. for 18 hours. The reaction mixture was concentrated to dryness under reduced pressure and purified via Biotage chromatography (silica, DCM: MeOH, gradient elution from 100:0 to 90:10) to give a colourless solid (47 mg, 52% yield). 1H-NMR (500 MHz, CDCl3) δ 7.63 (1H, s), 7.32 (2H, d), 7.27 (2H, d), 7.16-7.22 (3H, m), 7.09-7.16 (2H, m), 5.06 (1H, br s), 3.10 (2H, t), 2.68 (3H, s), 2.22-2.60 (6H, br m), 1.97-2.09 (1H, m), 1.72-1.84 (1H, m), 1.03-1.53 (9H, br m). LCMS (Method A) RT=5.34 min, M+H+=522.19.

Workup

  1. temperaturethe mixture heated to 80° C. under a nitrogen atmosphere for 2 hours
  2. temperaturethe mixture heated to 80° C. for 18 hours
  3. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  4. custompurified via Biotage chromatography (silica, DCM: MeOH, gradient elution from 100:0 to 90:10)

Sources & evidence

ORD record
ord-e4c6b39ada5341969b141d3da2013d8e
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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