Cyclohexylamine → HCID 11576187, compound

HRID 853900Notes

Reaction equation

HRID 853900 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[S:18]([C:21]2[CH:29]=[CH:28][C:27]3[N:26]4[CH2:30][C:31]([CH3:35])([CH3:34])[CH2:32][N:33]=[C:25]4[C:24]4([O:40]CCCO4)[C:23]=3[CH:22]=2)(=[O:20])=[O:19])(=O)=O)=CC=1.[CH:41]1([NH2:47])[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1>C1COCC1>[CH:41]1([NH:47][CH2:12][C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[S:18]([C:21]2[CH:29]=[CH:28][C:27]3[N:26]4[CH2:30][C:31]([CH3:34])([CH3:35])[CH2:32][N:33]=[C:25]4[C:24](=[O:40])[C:23]=3[CH:22]=2)(=[O:19])=[O:20])[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1

Participants

4

Reactant 2

HCID 7965Cyclohexylamine2×HCID 58932564HCID 58932564, compound

Product 1

HCID 11576187HCID 11576187, compoundYield 46.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of {(2S)-1-[(3′,3′-dimethyl-3′,4′-dihydro-2′H-spiro[1,3-dioxane-2,10′-pyrimido[1,2-a]indol]-8′-yl)sulfonyl]pyrrolidin-2-yl}methyl 4-methylbenzenesulfonate (0.100 g, 0.170 mmol) in THF (2 mL) was added cyclohexylamine (0.034 g, 0.340 mmol) and the reaction was stirred at 70° C. overnight. Additional cyclohexylamine (0.088 g, 0.850 mmol) was added to the reaction and stirred at 100° C. for 2 days. The reaction was quenched with water and extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered, concentrated and purified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (35/65). The resulting product was dissolved in CH2Cl2 (2 mL) and methanesulfonic acid (2 mL) was added and the solution was stirred at rt overnight. The reaction mixture was poured onto ice, basified to pH 11 with ammonium hydroxide and extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered, concentrated and purified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (35/65) to give the title compound as a yellow foam (0.036 g, 46%). NMR (400 Mz, DMSO-d6): consistent. MS: (ESI+) m/z 459.3 [M+H].

Workup

  1. stirringstirred at 100° C. for 2 days
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (35/65)
  8. dissolutionThe resulting product was dissolved in CH2Cl2 (2 mL)
  9. additionmethanesulfonic acid (2 mL) was added
  10. stirringthe solution was stirred at rt overnight
  11. additionThe reaction mixture was poured onto ice
  12. extractionextracted with EtOAc (3×)
  13. dry with materialThe combined organic extracts were dried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. custompurified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (35/65)

Sources & evidence

ORD record
ord-549ab2322cdd49308f9d728e9e2aba3e
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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