Fumaric Acid → 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide difumarate monohydrate

HRID 1182986Notes

Reaction equation

HRID 1182986 reaction equation
[CH:1]1([CH2:7][N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][C:12]([S:18]([NH:21][CH2:22][CH2:23][C@@H:24]4[CH2:28][CH2:27][CH2:26][N:25]4[CH3:29])(=[O:20])=[O:19])=[CH:13][CH:14]=3)[CH2:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34]>C(O)C>[OH2:19].[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34].[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34].[CH:1]1([CH2:7][N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][C:12]([S:18]([NH:21][CH2:22][CH2:23][C@@H:24]4[CH2:28][CH2:27][CH2:26][N:25]4[CH3:29])(=[O:19])=[O:20])=[CH:13][CH:14]=3)[CH2:9]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 444972Fumaric AcidHCID 115026452-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

Product 1

HCID 498537492-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide difumarate monohydrateYield 84%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-(Cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide (43.7 g, 104 mmol) was dissolved in 95% ethanol (200 mL) with warming on a steam bath. Fumaric acid (23.8 g, 203 mmol, 1.95 equivalents) was added, rinsing the flask with 95% ethanol (50 mL). The mixture was heated with swirling to near boiling on the steam bath until all of the fumaric acid dissolved. The solution was removed from the steam bath and allowed to stir at room temperature. When the temperature of the solution reached 48° C., it was seeded with previously isolated 2-(cyclohexyl methyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide difumarate monohydrate. The mixture was allowed to cool and by 27.7° C., it had largely set up. After standing over the weekend, the mixture was cooled in an ice bath. The solids were collected and washed with ice-cold 95% ethanol (175 mL). After air-drying overnight, the clumps were partially broken up to give a colorless solid: 58.4 g (84% yield).

Workup

  1. temperaturewith warming on a steam bath
  2. washrinsing the flask with 95% ethanol (50 mL)
  3. temperatureThe mixture was heated
  4. dissolutiondissolved
  5. customThe solution was removed from the steam bath
  6. customreached 48° C.
  7. temperatureto cool and by 27.7° C.
  8. temperaturethe mixture was cooled in an ice bath
  9. customThe solids were collected
  10. washwashed with ice-cold 95% ethanol (175 mL)
  11. customAfter air-drying overnight
  12. customto give a colorless solid

Sources & evidence

ORD record
ord-88689a5dfb074fad9ddc959fbf458004
Source dataset
uspto-grants-2014_03
Patent number
US08664245B2

Reaction notes

Loading…