Tributylphosphine → HCID 67529274, compound

HRID 1889593Notes

Reaction equation

HRID 1889593 reaction equation
[CH2:1]([C:3]1[S:28][C:6]2[N:7]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4[C:21]([C:26]#[N:27])=[CH:22][CH:23]=[CH:24][CH:25]=4)=[CH:16][CH:15]=3)[C:8](=[O:12])[NH:9][C:10](=[O:11])[C:5]=2[CH:4]=1)[CH3:2].[CH3:29][C:30]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([CH3:33])[CH2:31]O.C(P(CCCC)CCCC)CCC.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1.O>[CH2:1]([C:3]1[S:28][C:6]2[N:7]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4[C:21]([C:26]#[N:27])=[CH:22][CH:23]=[CH:24][CH:25]=4)=[CH:16][CH:15]=3)[C:8](=[O:12])[N:9]([CH2:29][C:30]([CH3:33])([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH3:31])[C:10](=[O:11])[C:5]=2[CH:4]=1)[CH3:2]

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 219535beta,beta-DimethylbenzeneethanolHCID 593517704'-[(6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl)methyl]biphenyl-2-carbonitrile

Product 1

HCID 67529274HCID 67529274, compoundYield 9.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4′-[(6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl)methyl]biphenyl-2-carbonitrile (1.5 g), 2-methyl-2-phenylpropan-1-ol (0.64 g), tributylphosphine (0.86 g) in THF (50 ml) was added ADDP (1.2 g) under ice-cooling, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give 4′-{[6-ethyl-3-(2-methyl-2-phenylpropyl)-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile (0.2 g). This was dissolved in dimethyl sulfoxide (2 mL), and the mixture was added to a mixture of hydroxylammonium chloride (0.27 g), sodium hydrogencarbonate (0.32 g) and dimethyl sulfoxide (20 mL), which had been stirred at 40° C. for 30 min in advance. The reaction mixture was stirred at 90° C. for 16 hr, diluted with chloroform, washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, dissolved in tetrahydrofuran (20 mL), N,N′-carbonyldiimidazole (0.075 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.070 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.073 g, 33%).

Workup

  1. temperaturecooling
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7d8853ff97f94d8abac63c5e3855474f
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

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