Morpholine → HCID 178452589, compound

HRID 1509088Notes

Reaction equation

HRID 1509088 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].[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1.O.[NH2:48][NH2:49]>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:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:26][C:25]4[C:24]5=[N:48][NH:49][C:35]([N:41]6[CH2:46][CH2:45][O:44][CH2:43][CH2:42]6)=[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)([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 24654Hydrazine hydrate (1:1)2×HCID 123658741HCID 123658741, compound

Product 1

HCID 178452589HCID 178452589, compoundYield 30%

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 morpholine (76 μl, 0.87 mmol) and the mixture heated to 80° C. under a nitrogen atmosphere for 2 hours. Hydrazine monohydrate (12.7 μl, 0.26 mmol) was added and the mixture heated to 80° C. for 1 hour. Further hydrazine monohydrate (72 μl, 1.48 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, cyclohexane:ethyl acetate, gradient elution from 92:2 to 100:0) to give a white solid (30 mg, 30% yield). 1H-NMR (500 MHz, CDCl3) δ 7.67 (1H, s), 7.31 (2H, d), 7.23-7.28 (2H, m), 7.18-7.24 (3H, m), 7.07-7.14 (2H, m), 4.95-5.44 (1H, br m), 3.82 (4H, t), 3.24 (2H, t), 3.21 (4H, t), 2.91 (2H, t), 2.19-2.64 (4H, br m), 1.97-2.09 (1H, m), 1.73-1.84 (1H, m), 1.10-1.46 (9H, br m). LCMS (Method A) RT=6.18 min, M+H+=578.24.

Workup

  1. temperaturethe mixture heated to 80° C. for 1 hour
  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, cyclohexane:ethyl acetate, gradient elution from 92:2 to 100:0)

Sources & evidence

ORD record
ord-8ad1d7bfe30f4fedacac834d1d33e3cd
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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