Methanesulfonic Acid → N-Methyl-3-(((2R)-1-methyl-2-pyrrolidinyl)methyl)-1H-indole-5-methanesulfonamide

HRID 651706Notes

Reaction equation

HRID 651706 reaction equation
C(O[CH2:9][N:10](C)[S:11]([CH2:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20](COCC1C=CC=CC=1)[CH:19]=[C:18]2[CH2:33][C@H:34]1[CH2:38][CH2:37][CH2:36][N:35]1[CH3:39])(=[O:13])=[O:12])C1C=CC=CC=1.CS(O)(=O)=O>O.[OH-].[OH-].[Pd+2]>[CH3:9][NH:10][S:11]([CH2:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][CH:19]=[C:18]2[CH2:33][C@H:34]1[CH2:38][CH2:37][CH2:36][N:35]1[CH3:39])(=[O:12])=[O:13]

Participants

5

Reactant 2

HCID 6395Methanesulfonic AcidHCID 53683333(R)-N-Benzyloxymethyl-1-[1-benzyloxymethyl-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indol-5-yl]-N-methylmethanesulfonamide

Product 1

HCID 132552N-Methyl-3-(((2R)-1-methyl-2-pyrrolidinyl)methyl)-1H-indole-5-methanesulfonamideYield 31.1%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 962WaterSolvent

Procedure

A mixture of (R)-N-Benzyloxymethyl-1-[1-benzyloxymethyl-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indol-5-yl]-N-methylmethanesulfonamide (from step (f), 300 mg, 0.5 mmol) and methanesulfonic acid (60 mg, 0.6 mmol) in water (5 ml) was hydrogenated over Pearlman's catalyst (300 mg) at 60° C. and at 345 kPa (50 psi) for 18 hr. The solution was then filtered through a pad of celite (trade mark) and the filtrate was partitioned between saturated sodium bicarbonate (25 ml) and dichloromethane (3×50 ml). The combined organic extract was then evaporated in vacuo and the residue was dissolved in a mixture of THF and water (1:1) (10 ml). A solution of Triton B (40% w.w. in methanol) (0.2 ml, 0.44 mmol) was then added dropwise and the solution was then refluxed for 2 hr. The solution was then cooled to ambient temperature before being poured into water (10 ml) and extracted with dichloromethane (3×25 ml). The combined organic extracts were evaporated in vacuo to give a yellow film. This was then triturated with IMS (5 ml) and tie solid was filtered in vacuo and dried at 50° C. overnight to yield the title compound (50 mg, 29%) as a white solid. m.p. 209-231° C.

Workup

  1. filtrationThe solution was then filtered through a pad of celite (trade mark)
  2. customthe filtrate was partitioned between saturated sodium bicarbonate (25 ml) and dichloromethane (3×50 ml)
  3. extractionThe combined organic extract
  4. customwas then evaporated in vacuo
  5. dissolutionthe residue was dissolved in a mixture of THF and water (1:1) (10 ml)
  6. additionA solution of Triton B (40% w.w. in methanol) (0.2 ml, 0.44 mmol) was then added dropwise
  7. temperaturethe solution was then refluxed for 2 hr
  8. additionbefore being poured into water (10 ml)
  9. extractionextracted with dichloromethane (3×25 ml)
  10. customThe combined organic extracts were evaporated in vacuo
  11. customto give a yellow film
  12. customThis was then triturated with IMS (5 ml)
  13. filtrationwas filtered in vacuo
  14. customdried at 50° C. overnight

Sources & evidence

ORD record
ord-82b921985b484b79b345398863dcb775
Source dataset
uspto-grants-2001_08
Patent number
US06281357B1

Reaction notes

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