(R)-7-Bromo-5-(methylaminosulfonylmethyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole → N-Methyl-3-(((2R)-1-methyl-2-pyrrolidinyl)methyl)-1H-indole-5-methanesulfonamide

HRID 744157Notes

Reaction equation

HRID 744157 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:18][S:19]([NH:22][CH3:23])(=[O:21])=[O:20])[CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH3:17].[H][H]>[OH-].[OH-].[Pd+2]>[CH3:23][NH:22][S:19]([CH2:18][C:4]1[CH:5]=[C:6]2[C:10](=[CH:2][CH:3]=1)[NH:9][CH:8]=[C:7]2[CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH3:17])(=[O:20])=[O:21]

Participants

4

Reactant 2

HCID 10905439(R)-7-Bromo-5-(methylaminosulfonylmethyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indoleHCID 178418361HCID 178418361, compound

Product 1

HCID 132552N-Methyl-3-(((2R)-1-methyl-2-pyrrolidinyl)methyl)-1H-indole-5-methanesulfonamideYield 58%

Reagents, catalysts & solvents 1

HCID 9942167Palladium hydroxideCatalyst

Procedure

A solution of (R)-7-bromo-5-(methylaminosulfonylmethyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole (193 g) in industrial methylated spirit (950 mL) containing Pearlman's catalyst (47.6 g total) was exposed to hydrogen gas (50 psi). The catalyst was then filtered through an Arbacel pad, washing with hot industrial methylated spirit (2×100 mL) and the combined filtrate and washings evaporated in vacuo to an organic residue. The filtered solids (catalyst+filter aid) were then reslurried in 2N hydrochloric acid (500 mL) then refiltered (through Arbacel)and the filtrand washed with 2N hydrochloric acid (4×250 mL) and water (2×100 mL). The aqueous filtrate and washes were combined with the organic residue and then once washed with ethyl acetate (1000 mL). The aqueous solution was chilled then made basic by addition of 40% aqueous sodium hydroxide solution precipitating the title compound as a pale-yellow solid. This solid was filtered, washed with water (2×100 mL) and dried in vacuo to give the title compound (89.9 g). TLC (methyl iso-butyl ketone/acetic acid/water 2:1:1 Top phase): Rf=0.23. 1H NMR (d6 DMSO) δ10.85 (s, 1H), 7.5 (s, 1H), 7.3 (d, 1H), 7.15 (s, 1H), 7.05 (d, 1H), 6.8 (q, 1H), 4.35 (s, 2H), 3.0 (m, 2H), 2.55-2.4 (d, 3H and m, 2H), 2.35 (s, 3H), 2.1 (m, 1H), 1.7-1.4 (m, 4H).

Workup

  1. filtrationThe catalyst was then filtered through an Arbacel pad
  2. washwashing with hot industrial methylated spirit (2×100 mL)
  3. customthe combined filtrate and washings evaporated in vacuo to an organic residue
  4. filtrationThe filtered solids (catalyst+filter aid)
  5. washwashed with 2N hydrochloric acid (4×250 mL) and water (2×100 mL)
  6. washonce washed with ethyl acetate (1000 mL)
  7. temperatureThe aqueous solution was chilled
  8. additionthen made basic by addition of 40% aqueous sodium hydroxide solution
  9. customprecipitating the title compound as a pale-yellow solid
  10. filtrationThis solid was filtered
  11. washwashed with water (2×100 mL)
  12. customdried in vacuo

Sources & evidence

ORD record
ord-d01e9dcf5d204047b4f2d9f12a72925a
Source dataset
uspto-grants-1996_09
Patent number
US05559129

Reaction notes

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