Trifluoroacetic acid → (S)-1-(7,8-Difluoro-1,2,3,4-tetrahydrocyclopent[b]indol-4-yl)-2-propylamine fumarate

HRID 49426Notes

Reaction equation

HRID 49426 reaction equation
C(OC([NH:8][C@@H:9]([CH3:25])[CH2:10][N:11]1[C:19]2[CH:18]=[CH:17][C:16]([F:20])=[C:15]([F:21])[C:14]=2[C:13]2[CH2:22][CH2:23][CH2:24][C:12]1=2)=O)(C)(C)C.FC(F)(F)C(O)=O.[OH-].[Na+].[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39]>ClCCl.CC(O)C>[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39].[F:20][C:16]1[CH:17]=[CH:18][C:19]2[N:11]([CH2:10][C@@H:9]([NH2:8])[CH3:25])[C:12]3[CH2:24][CH2:23][CH2:22][C:13]=3[C:14]=2[C:15]=1[F:21]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 444972Fumaric AcidHCID 67551092(S)-4-[2-(tert-butoxycarbonylamino)propyl]-7,8-difluoro-1,2,3,4-tetrahydrocyclopent[b]indole

Product 1

HCID 20637262(S)-1-(7,8-Difluoro-1,2,3,4-tetrahydrocyclopent[b]indol-4-yl)-2-propylamine fumarateYield 220.8%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-4-[2-(tert-butoxycarbonylamino)propyl]-7,8-difluoro-1,2,3,4-tetrahydrocyclopent[b]indole (0.4 g, 1.1 mmol) and trifluoroacetic acid (5 mL) in dichloromethane (15 mL) was stirred at room temperature for 1 h. The mixture was made basic by the addition of aqueous sodium hydroxide solution (2 N), then extracted with dichloromethane (3×50 mL). The organic extracts were combined, dried (magnesium sulfate), filtered and concentrated in vacuo to give an orange oil. The oil was dissolved in 2-propanol (5 mL) and the solution was heated to boiling then fumaric acid (0.38 g, 3.3 mmol) was added. The mixture was cooled to room temperature and filtered The filter-cake was washed (2-propanol, ether) and dried in vacuo to give the title compound (0.89 g, 68%) as a pale orange solid. mp. 154-156° C. (dec.); NMR δH (400 MHz, DMSO-d6) 1.13 (3H, d, J 7 Hz), 2.43-2.52 (2H, m), 2.78-2.94 (4H, m), 3.5-3.57 (1H, m), 4.13 (1H, d, J 8 Hz), 4.29 (1H, dd, J 6.5 Hz), 6.55 (2H, s), 7.01-7.10 (1H, m) and 7.26-7.31 (1H, m).

Workup

  1. extractionextracted with dichloromethane (3×50 mL)
  2. dry with materialdried (magnesium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give an orange oil
  6. temperaturethe solution was heated
  7. filtrationfiltered The filter-cake
  8. washwas washed (2-propanol, ether)
  9. customdried in vacuo

Sources & evidence

ORD record
ord-440c0d7b02504fcc9c25d5b6efe399a3
Source dataset
uspto-grants-2004_03
Patent number
US06706750B1

Reaction notes

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