N-Methyl dicyclohexylamine → HCID 66816141, compound

HRID 1755003Notes

Reaction equation

HRID 1755003 reaction equation
[CH:1]([S:3]([N:6]1[CH2:27][CH2:26][C:9]2([N:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[C:16]([C:21]([F:24])([F:23])[F:22])[CH:15]=3)[NH:11][C:10]2=[O:25])[CH2:8][CH2:7]1)(=[O:5])=[O:4])=[CH2:2].Br[C:29]1[C:41]([CH3:42])=[CH:40][C:32]([O:33][CH2:34][CH2:35][CH:36]([OH:39])[CH2:37][OH:38])=[CH:31][C:30]=1[CH3:43].F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CN(C1CCCCC1)C1CCCCC1.[NH4+].[Cl-]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CN1C(=O)CCC1>[OH:39][CH:36]([CH2:37][OH:38])[CH2:35][CH2:34][O:33][C:32]1[CH:31]=[C:30]([CH3:43])[C:29](/[CH:2]=[CH:1]/[S:3]([N:6]2[CH2:7][CH2:8][C:9]3([N:13]=[C:12]([C:14]4[CH:19]=[CH:18][C:17]([F:20])=[C:16]([C:21]([F:22])([F:23])[F:24])[CH:15]=4)[NH:11][C:10]3=[O:25])[CH2:26][CH2:27]2)(=[O:5])=[O:4])=[C:41]([CH3:42])[CH:40]=1

Participants

8

Reactant 5

HCID 24210N-Methyl dicyclohexylamineHCID 25517Ammonium ChlorideHCID 44558591Tri-t-butylphosphine fluoroborateHCID 66817256HCID 66817256, compoundHCID 66817493HCID 66817493, compound

Product 1

HCID 66816141HCID 66816141, compoundYield 49.1%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

8-Ethenesulfonyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-1,3,8-triaza-spiro[4.5]dec-1-en-4-one (57.6 mg, 0.142 mmol), 4-(4-bromo-3,5-dimethyl-phenoxy)-butane-1,2-diol (49.3 mg, 0.170 mmol), bis(dibenzylideneacetone)palladium(0) (8 mg, 0.014 mmol) and tri-tert-butylphosphine tetrafluoroborate (4 mg, 0.014 mmol) were placed in a vial. NMP (0.5 ml) and N-methyldicyclohexylamine (36.1 μl, 0.170 mmol) were sequentially added in a nitrogen atmosphere, and the mixture was heated with stirring at 100° C. for 2.5 hours. A saturated aqueous NH4Cl solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was sequentially washed with water and saturated brine and then concentrated under reduced pressure. The resulting residue was purified by thin layer chromatography (ethyl acetate:dichloromethane:methanol=10:10:1) to give 8-{(E)-2-[4-(3,4-dihydroxy-butoxy)-2,6-dimethyl-phenyl]-ethenesulfonyl}-2-(4-fluoro-3-trifluoromethyl-phenyl)-1,3,8-triaza-spiro[4.5]dec-1-en-4-one (42.8 mg, 49%).

Workup

  1. temperaturethe mixture was heated
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was sequentially washed with water and saturated brine
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by thin layer chromatography (ethyl acetate:dichloromethane:methanol=10:10:1)

Sources & evidence

ORD record
ord-1663a1300b3a4ab6aa58f1cdab64a56f
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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