Dimethylamine → HCID 58717241, compound

HRID 1244537Notes

Reaction equation

HRID 1244537 reaction equation
C(O[C:4]([C:6]1[C:14]2[CH2:13][CH2:12][N:11]([C:15]3[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][CH:16]=3)[C:10](=[O:23])[C:9]=2[N:8]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[N:7]=1)=[O:5])C.[CH3:32][NH:33][CH3:34].[CH3:35][S:36](Cl)(=[O:38])=[O:37].C([N:42](CC)CC)C>CO.C(Cl)(Cl)Cl.Cl>[CH3:32][N:33]([C:21](=[N:22][S:36]([CH3:35])(=[O:38])=[O:37])[C:18]1[CH:17]=[CH:16][C:15]([N:11]2[CH2:12][CH2:13][C:14]3[C:6]([C:4]([NH2:42])=[O:5])=[N:7][N:8]([C:24]4[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=4)[C:9]=3[C:10]2=[O:23])=[CH:20][CH:19]=1)[CH3:34]

Participants

7

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 69593723HCID 69593723, compound

Product 1

HCID 58717241HCID 58717241, compoundYield 26.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 21584188Chloroform methanolSolvent

Procedure

6-(4-Cyano-phenyl)-1-(4-methoxy-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester (0.100 g, 0.240 mmol) was dissolved in 1:1 methanol/chloroform (20 mL), and hydrogen chloride gas was bubbled through the solution for 15 min, and it was then tightly capped and sealed. The reaction was stirred overnight at rt and then concentrated to dryness. The crude intermediate was dissolved in methanol (10 mL), and 2M dimethylamine (0.012 mL, 2.40 mmol) was added. The reaction was tightly capped and sealed and stirred overnight at rt. The reaction was concentrated and redissolved in methylene chloride (6 mL). Methanesulfonylchloride (0.03 mL, 0.360 mmol) and triethylamine (0.08 mL, 0.600 mmol) were added to the reaction. The reaction was stirred at rt overnight. The reaction was then concentrated and purified by flash chromatography using 0–100% ethyl acetate/hexanes as the eluent followed by methanol. The methanesulfonamide intermediate was dissolved in 5% ammonia/ethylene glycol and heated at 80° C. in a sealed tube for 2 hr. The reaction was quenched with water (50 mnL), extracted with ethyl acetate (3×50 mL), washed with brine (50 mL), dried with MgSO4, and concentrated. Purification by reverse phase HPLC and freeze-drying afforded the title compound (0.032 g, 26%): 1H NMR (CHCl3) δ 7.83–7.35 (m, 6H), 6.99–6.93 (m, 3H), 6.36 (bs, 1H), 4.18 (t, j=6.6 Hz, 2H), 3.83 (s, 3H), 3.37 (t, j=6.8 Hz, 2H), 3.19 (s, 3H), 2.93 (s, 3H), 2.81 (s, 3H) ppm; Mass Spec 511.3 (M+H)+.

Workup

  1. customwas bubbled through the solution for 15 min
  2. customit was then tightly capped
  3. customsealed
  4. concentrationconcentrated to dryness
  5. dissolutionThe crude intermediate was dissolved in methanol (10 mL)
  6. customThe reaction was tightly capped
  7. customsealed
  8. stirringstirred overnight at rt
  9. concentrationThe reaction was concentrated
  10. dissolutionredissolved in methylene chloride (6 mL)
  11. stirringThe reaction was stirred at rt overnight
  12. concentrationThe reaction was then concentrated
  13. custompurified by flash chromatography
  14. dissolutionThe methanesulfonamide intermediate was dissolved in 5% ammonia/ethylene glycol
  15. temperatureheated at 80° C. in a sealed tube for 2 hr
  16. customThe reaction was quenched with water (50 mnL)
  17. extractionextracted with ethyl acetate (3×50 mL)
  18. washwashed with brine (50 mL)
  19. dry with materialdried with MgSO4
  20. concentrationconcentrated
  21. customPurification by reverse phase HPLC
  22. customfreeze-drying

Sources & evidence

ORD record
ord-a7b91c5978624b6a8ffdca5032fdb749
Source dataset
uspto-grants-2006_10
Patent number
US07122557B2

Reaction notes

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