Diisopropylethylamine → HCID 178438608, compound

HRID 519815Notes

Reaction equation

HRID 519815 reaction equation
[O:1]=[C:2]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]2[N:26]=[CH:27][CH:28]=[C:4]2[N:3]1[C@H:29]1[CH2:34][CH2:33][C@H:32]([O:35][CH2:36][C:37](=[O:39])[CH3:38])[CH2:31][CH2:30]1.[CH:40](N(C(C)C)CC)(C)C.FC(F)(F)S(O[Si:55]([C:58]([CH3:61])([CH3:60])[CH3:59])([CH3:57])[CH3:56])(=O)=O.C(=O)([O-])O.[Na+]>C(Cl)Cl.C(OCC)(=O)C>[Si:55]([O:39][C:37]1([CH2:36][O:35][C@H:32]2[CH2:31][CH2:30][C@H:29]([N:3]3[C:2](=[O:1])[C:7]([CH2:8][C:9]4[CH:10]=[CH:11][C:12]([C:15]5[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=5)=[CH:13][CH:14]=4)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]4[N:26]=[CH:27][CH:28]=[C:4]34)[CH2:34][CH2:33]2)[CH2:40][CH2:38]1)([C:58]([CH3:61])([CH3:60])[CH3:59])([CH3:57])[CH3:56]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 516892Sodium BicarbonateHCID 178438630HCID 178438630, compound

Product 1

HCID 178438608HCID 178438608, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4′-({5-oxo-4-[trans-4-(2-oxopropoxy)cyclohexyl]-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.93 g) and diisopropylethylamine (0.77 mL) in methylene chloride (10 mL) was added dropwise tert-butyldimethylsilyl trifluoromethanesulfonate (1.02 mL) at −78° C., and the mixture was stirred for 3 hr while warming to 0° C. To the reaction mixture were added ethyl acetate and saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was crudely purified by silica gel column chromatography, and dissolved in methylene chloride (5 mL), and the mixture was added dropwise to a solution of diethylzinc (1 M hexane solution, 7.5 mL) and chloroiodomethane (0.55 mL) in methylene chloride (10 mL) at 0° C., and the mixture was stirred for 2 hr. To the reaction mixture were added ethyl acetate and then saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.67 g, 68%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was crudely purified by silica gel column chromatography
  6. dissolutiondissolved in methylene chloride (5 mL)
  7. additionthe mixture was added dropwise to a solution of diethylzinc (1 M hexane solution, 7.5 mL) and chloroiodomethane (0.55 mL) in methylene chloride (10 mL) at 0° C.
  8. stirringthe mixture was stirred for 2 hr
  9. additionTo the reaction mixture were added ethyl acetate
  10. extractionsaturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate
  11. washThe organic layer was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated
  14. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-eeb827d1688b40389065b95674fa1b25
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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