Diisopropylamine → HCID 23503252, compound

HRID 1835147Notes

Reaction equation

HRID 1835147 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH3:13][N:14]1[C:19](=[O:20])[C:18]2[CH:21]=[C:22]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[S:23][C:17]=2[C:16]([CH2:31][CH:32]([CH3:34])[CH3:33])=[N:15]1.CC1C=CC(S(=O)([S:44][CH2:45][CH2:46][CH2:47][O:48][Si](C(C)(C)C)(C)C)=O)=CC=1>O1CCCC1>[OH:48][CH2:47][CH2:46][CH2:45][S:44][C:21]1[C:18]2[C:19](=[O:20])[N:14]([CH3:13])[N:15]=[C:16]([CH2:31][CH:32]([CH3:34])[CH3:33])[C:17]=2[S:23][C:22]=1[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 23503259HCID 23503259, compoundHCID 23503276HCID 23503276, compoundHCID 178418339Butyllithium

Product 1

HCID 23503252HCID 23503252, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of butyl lithium in hexanes (2.5M, 1.3 ml) was added to a solution of diisopropylamine (0.45 ml) in tetrahydrofuran (6 ml) at 0° C. under nitrogen. After 30 minutes, 5 ml of the resulting solution was added to a solution of 5-methyl-7-(2-methylpropyl)-2-phenylmethylthieno[2,3-d]pyridazin-4(5H)-one (example 15, 0.50 g) and S-[3-{[(1,1-dimethylethyl)dimethylsilyl]oxy}propyl] 4methylbenzenesulfonothioate, (J. Med. Chem. 1995, 38, 2557., 0.85 g) in tetrahydrofuran (10 ml) at −78° C. under nitrogen. The reaction mixture was warmed to room temperature, quenched with saturated aqueous ammonium chloride solution (25 ml) and extracted with ethyl acetate (50 ml). The organic extracts were washed twice with saturated aqueous ammonium chloride solution, twice with saturated sodium hydrogen carbonate solution, then with brine, dried, filtered and evaporated. The residue was dissolved in acetonitrile (20 ml) and treated with 40% hydrofluoric acid (1 ml). After 16 hours, saturated sodium hydrogen carbonate solution (50 ml) was added and the mixture was extracted with ethyl acetate (50 ml). The organic extracts were washed with brine, dried, filtered and evaporated. The residue was purified by column chromatography, eluting with ethyl acetate:isohexane (1:2 then 1:1) to give the title compound (0.51 g) as a solid.

Workup

  1. customquenched with saturated aqueous ammonium chloride solution (25 ml)
  2. extractionextracted with ethyl acetate (50 ml)
  3. washThe organic extracts were washed twice with saturated aqueous ammonium chloride solution, twice with saturated sodium hydrogen carbonate solution
  4. dry with materialwith brine, dried
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe residue was dissolved in acetonitrile (20 ml)
  8. additiontreated with 40% hydrofluoric acid (1 ml)
  9. waitAfter 16 hours
  10. additionsaturated sodium hydrogen carbonate solution (50 ml) was added
  11. extractionthe mixture was extracted with ethyl acetate (50 ml)
  12. washThe organic extracts were washed with brine
  13. customdried
  14. filtrationfiltered
  15. customevaporated
  16. customThe residue was purified by column chromatography
  17. washeluting with ethyl acetate:isohexane (1:2

Sources & evidence

ORD record
ord-68dc712198f246abad214075dc9528bf
Source dataset
uspto-grants-2004_08
Patent number
US06770646B2

Reaction notes

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