Hydrochloric Acid → HCID 66668997, compound

HRID 1617985Notes

Reaction equation

HRID 1617985 reaction equation
Cl.[CH3:2][C:3]1[CH:8]=[C:7]([C:9](=[O:38])[CH2:10][C@H:11]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH:26]=3)=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])[CH:6]=[CH:5][N:4]=1.C(N(CC)C(C)C)(C)C.[CH3:48][S:49](Cl)(=[O:51])=[O:50]>>[CH3:2][C:3]1[CH:8]=[C:7]([C:9](=[O:38])[CH2:10][C@H:11]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH2:30][CH2:29][N:28]([S:49]([CH3:48])(=[O:51])=[O:50])[CH2:27][CH:26]=3)=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])[CH:6]=[CH:5][N:4]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 66668618HCID 66668618, compound

Product 1

HCID 66668997HCID 66668997, compoundYield 25.2%

Conditions

Temperature
50 °C

Procedure

Hydrogen chloride solution (4 M in 1,4-dioxane, 2 mL) was added to a solution of (R)-tert-butyl 4-(4-(3-(2-methylpyridin-4-yl)-3-oxo-1-o-tolylpropyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (example 372, step 1; 100 mg, 201 μmol). The reaction mixture was heated at 50° C. for 17 h, then partitioned between sat. aq. sodium hydrogencarbonate solution and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and evaporated. The residue was dissolved in dichloromethane (5 mL), then cooled to 0° C. and treated with N,N-diisopropylethylamine (78 mg, 604 μmol) and methanesulfonyl chloride (34.6 mg, 302 μmol). The ice bath was removed, then after 3 h the reaction mixture was partitioned between sat. aq. ammonium chloride solution and dichloromethane. The organic layer was washed with brine, dried over sodium sulfate, filtered, and evaporated. Chromatography (SiO2; heptane-ethyl acetate gradient) produced the title compound (24 mg, 25%). White foam, MS (ESI+): m/z=475.1 ([M+H]+).

Workup

  1. custompartitioned between sat. aq. sodium hydrogencarbonate solution and ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe residue was dissolved in dichloromethane (5 mL)
  7. temperaturecooled to 0° C.
  8. customThe ice bath was removed
  9. customafter 3 h the reaction mixture was partitioned between sat. aq. ammonium chloride solution and dichloromethane
  10. washThe organic layer was washed with brine
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-cbc2b374fa394eab8dacc1a5baf5f5a3
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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