N-Methyl dicyclohexylamine → HCID 90224890, compound

HRID 1487096Notes

Reaction equation

HRID 1487096 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]1[CH:4]=[C:5]([C:9]2[NH:13][C:12](=[O:14])[C:11]3([CH2:19][CH2:18][N:17]([S:20]([CH:23]=[CH2:24])(=[O:22])=[O:21])[CH2:16][CH2:15]3)[N:10]=2)[CH:6]=[CH:7][CH:8]=1.Br[C:28]1[C:33]([CH3:34])=[CH:32][C:31]([N:35]2[C:39]([CH3:41])([CH3:40])[C:38](=[O:42])[NH:37][C:36]2=[O:43])=[CH:30][C:29]=1[CH3:44].F[B-](F)(F)F.[H+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CN(C1CCCCC1)C1CCCCC1>CN1CCCC1=O.[Pd]>[CH3:34][C:33]1[CH:32]=[C:31]([N:35]2[C:39]([CH3:40])([CH3:41])[C:38](=[O:42])[NH:37][C:36]2=[O:43])[CH:30]=[C:29]([CH3:44])[C:28]=1/[CH:24]=[CH:23]/[S:20]([N:17]1[CH2:16][CH2:15][C:11]2([N:10]=[C:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:25])[F:26])[CH:4]=3)[NH:13][C:12]2=[O:14])[CH2:19][CH2:18]1)(=[O:22])=[O:21]

Participants

7

Reactant 4

HCID 24210N-Methyl dicyclohexylamineHCID 66827510HCID 66827510, compoundHCID 90224863HCID 90224863, compoundHCID 118705180Tris(tert-butyl)phosphonium tetrafluoroborate

Product 1

HCID 90224890HCID 90224890, compoundYield 82.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(3-(trifluoromethyl)phenyl)-8-(vinylsulfonyl)-1,3,8-triazaspiro[4.5]deca-1-en-4-one (150 mg, 0.387 mmol) synthesized according to the method described in Schemes 2, 3, and 12 of WO2010/126030(A1), 1-(4-bromo-3,5-dimethylphenyl)-5,5-dimethylimidazolidine-2,4-dione (169 mg, 0.542 mmol), bis(dibenzylidineacetone) palladium (45 mg, 0.077 mmol), tri-tert-butylphosphine tetrafluoroboric acid (22 mg, 0.077 mmol), and methyldicyclohexylamine (0.123 mL, 0.581 mmol) in N-methyl-2-pyrrolidone (0.97 mL) was stirred at 100° C. for one hour under nitrogen atmosphere. The reaction mixture was cooled, quenched with water, and then extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate-hexane) to afford (E)-1-(3,5-dimethyl-4-(2-((4-oxo-2-(3-(trifluoromethyl)phenyl)-1,3,8-triazaspiro[4.5]deca-1-en-8-yl)sulfonyl)vinyl)phenyl)-5,5-dimethylimidazolidine-2,4-dione (197 mg, 82%).

Workup

  1. customsynthesized
  2. temperatureThe reaction mixture was cooled
  3. customquenched with water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-b4e4233854c945a598d2d209cd5cdc3d
Source dataset
uspto-grants-2016_08
Patent number
US09428505B2

Reaction notes

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