4-Methylmorpholine → 4'-{[6-ethyl-3-(2-hydroxy-1-methylethyl)-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile

HRID 1889365Notes

Reaction equation

HRID 1889365 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][N:16]2[C:21]3[S:22][C:23]([CH2:25][CH3:26])=[CH:24][C:20]=3[C:19](=[O:27])[N:18]([CH:28]([CH3:33])[C:29](OC)=[O:30])[C:17]2=[O:34])=[CH:11][CH:10]=1)#[N:2].CN1CCOCC1.C(Cl)(=O)OCC.[BH4-].[Na+]>CO.O1CCCC1>[CH2:25]([C:23]1[S:22][C:21]2[N:16]([CH2:15][C:12]3[CH:13]=[CH:14][C:9]([C:4]4[C:3]([C:1]#[N:2])=[CH:8][CH:7]=[CH:6][CH:5]=4)=[CH:10][CH:11]=3)[C:17](=[O:34])[N:18]([CH:28]([CH3:33])[CH2:29][OH:30])[C:19](=[O:27])[C:20]=2[CH:24]=1)[CH3:26]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 59351649methyl 2-[1-[(2'-cyanobiphenyl-4-yl)methyl]-6-ethyl-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidin-3(2H)-yl]propanoate

Product 1

HCID 593516824'-{[6-ethyl-3-(2-hydroxy-1-methylethyl)-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrileYield 70.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

To a mixture of methyl 2-[1-[(2′-cyanobiphenyl-4-yl)methyl]-6-ethyl-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidin-3(2H)-yl]propanoate (3 g), N-methylmorpholine (0.86 mL) and tetrahydrofuran (50 mL) was added ethyl chlorocarbonate (0.75 mL) at 0° C., and the mixture was stirred at the same temperature for 2 hr. The reaction mixture was cooled to −15° C., sodium borohydride (0.74 g) and methanol (12 mL) were added, and the mixture was allowed to gradually warm to room temperature. The reaction mixture was extracted with saturated aqueous ammonium chloride solution and ethyl acetate. The ethyl acetate layer was washed with 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 a colorless amorphous solid (2 g, 69%).

Workup

  1. temperatureto gradually warm to room temperature
  2. extractionThe reaction mixture was extracted with saturated aqueous ammonium chloride solution and ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9bd5a3e07e6444e49c2556fb0296562b
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

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