2-Methyl-2-butanol → Dasabuvir

HRID 1499360Notes

Reaction equation

HRID 1499360 reaction equation
P.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(O)(CC)(C)C.CS(O[C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([C:31]3[CH:36]=[C:35]([N:37]4[CH:42]=[CH:41][C:40](=[O:43])[NH:39][C:38]4=[O:44])[CH:34]=[C:33]([C:45]([CH3:48])([CH3:47])[CH3:46])[C:32]=3[O:49][CH3:50])[CH:27]=2)[CH:22]=1)(=O)=O.[CH3:51][S:52]([NH2:55])(=[O:54])=[O:53]>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:45]([C:33]1[C:32]([O:49][CH3:50])=[C:31]([C:26]2[CH:27]=[C:28]3[C:23](=[CH:24][CH:25]=2)[CH:22]=[C:21]([NH:55][S:52]([CH3:51])(=[O:54])=[O:53])[CH:30]=[CH:29]3)[CH:36]=[C:35]([N:37]2[CH:42]=[CH:41][C:40](=[O:43])[NH:39][C:38]2=[O:44])[CH:34]=1)([CH3:48])([CH3:47])[CH3:46]

Participants

7

Reactant 5

HCID 64052-Methyl-2-butanol2×HCID 24404PhosphineHCID 62657Potassium Phosphate, TribasicHCID 72879MethanesulfonamideHCID 866938706-(3-tert-Butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl methanesulfonate

Product 1

HCID 56640146Dasabuvir

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (0.0037 g, 4.04 mmol), di-tertbutyl 2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (0.0047 g, 9.7 μmol) and milled potassium phosphate tribasic (0.094 g, 0.445 mmol) were charged to a 40-mL reaction vial inside an inert atmosphere glove box. tert-Amyl alcohol (1.0 mL) was added, the contents were heated to 80 ° C. and stirred at this temperature for 30 minutes. The reaction mixture was cooled down to room temperature. 6-(3-tert-Butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl methanesulfonate (0.2 g, 0.404 mmol), methanesulfonamide (0.046 g, 0.485 mmol) and tert-amyl alcohol (1.5 mL) were added to a 40-mL reaction vial. The reaction temperature was raised to 110 ° C., and the contents were stirred for 14 hours. HPLC analysis of the reaction mixture showed that the titled compound was formed in 7 area % at 210 mn.

Workup

  1. additionwere charged to a 40-mL reaction vial inside an inert atmosphere glove box
  2. temperatureThe reaction mixture was cooled down to room temperature
  3. temperatureThe reaction temperature was raised to 110 ° C.
  4. stirringthe contents were stirred for 14 hours

Sources & evidence

ORD record
ord-b289201f1b034a3492d9f8b5bcf8def0
Source dataset
uspto-grants-2015_12
Patent number
US09200021B2

Reaction notes

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