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4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → tert-butyl {5-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-amino)prop-1-en-1-yl]-2,3-dihydro-1H-inden-1-yl}carbamate

HRID 339130
Notes
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Reaction equation

HRID 339130 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[C:17]2[C:12](=[CH:13][C:14](/[CH:18]=[CH:19]/[C:20](O)=[O:21])=[CH:15][CH:16]=2)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:23][C:24]([F:38])([F:37])[CH:25]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=1)[NH2:26].[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CN(C=O)C.C(OCC)(=O)C>[O:21]=[C:20]([NH:26][CH:25]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:34])([F:35])[F:36])[CH:28]=1)[C:24]([F:38])([F:37])[F:23])/[CH:19]=[CH:18]/[C:14]1[CH:13]=[C:12]2[C:17](=[CH:16][CH:15]=1)[CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10][CH2:11]2
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 438251722,2,2-Trifluoro-1-(3-(trifluoromethyl)phenyl)ethanamineHCID 58248007(2E)-3-{1-[(tert-butoxycarbonyl)amino]-2,3-dihydro-1H-inden-5-yl}acrylic acid

Product 1

HCID 86653077tert-butyl {5-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-amino)prop-1-en-1-yl]-2,3-dihydro-1H-inden-1-yl}carbamateYield 89.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

1.5 g (4.95 mmol) of (2E)-3-{1-[(tert-butoxycarbonyl)amino]-2,3-dihydro-1H-inden-5-yl}acrylic acid and 1.2 g (4.95 mmol) of 2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethanamine were dissolved in 100 ml of DMF, 1.5 g (5.44 mmol) of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride were added, and the reaction mixture was heated to 50° C. overnight. The reaction solution was diluted with ethyl acetate, washed with sat. NaHCO3 solution, 1N hydrochloric acid and sat. sodium chloride solution, dried over sodium sulphate, filtered and concentrated. Chromatographic purification gave 2.3 g (4.45 mmol) of tert-butyl {5-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}amino)prop-1-en-1-yl]-2,3-dihydro-1H-inden-1-yl}carbamate (87%).

Workup

  1. washwashed with sat. NaHCO3 solution, 1N hydrochloric acid and sat. sodium chloride solution
  2. dry with materialdried over sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customChromatographic purification

Sources & evidence

ORD record
ord-20823a31565844d89eae1c0729912783
Source dataset
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08889878B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes