Hydrochloric Acid → tert-butyl 2-{[2-amino-3-(aminocarbonyl)-9H-pyrido[2,3-b]indol-9-yl]methyl}pyrrolidine-1-carboxylate

HRID 421660Notes

Reaction equation

HRID 421660 reaction equation
[NH2:1][C:2]1[C:3]([C:15]([NH2:17])=[O:16])=[CH:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][C:6]=2[N:14]=1.[OH-].[Na+].Br[CH2:21][CH:22]1[CH2:26][CH2:25][CH2:24][N:23]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].Cl>CN(C)C=O.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O>[NH2:1][C:2]1[C:3]([C:15]([NH2:17])=[O:16])=[CH:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:7]([CH2:21][CH:22]3[CH2:26][CH2:25][CH2:24][N:23]3[C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[C:6]=2[N:14]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 14821711tert-Butyl 2-(bromomethyl)pyrrolidine-1-carboxylateHCID 152709842-amino-9H-pyrido[2,3-b]indole-3-carboxamide

Product 1

HCID 59513632tert-butyl 2-{[2-amino-3-(aminocarbonyl)-9H-pyrido[2,3-b]indol-9-yl]methyl}pyrrolidine-1-carboxylateYield 24.4%

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-amino-9H-pyrido[2,3-b]indole-3-carboxamide (5, 50 mg, 0.2 mmol) in N,N-dimethylformamide (0.5 mL) was added powdered sodium hydroxide (12 mg, 0.31 mmol) and tetrabutylammonium hydrogen sulfate (3 mg, 0.009 mmol). The mixture was stirred at room temperature for 30 min then tert-butyl 2-(bromomethyl)pyrrolidine-1-carboxylate (67 mg, 0.25 mmol) was added. The resulting mixture was stirred at room temperature for 4 days. Water (5 ml) was added to the mixture, followed by HCl (3% aqueous, 1 mL). The mixture was extracted with ethyl acetate (3×30 ml). The extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (12 g silica, methylene chloride to 90/10 methylene chloride/methanol gradient) to yield tert-butyl 2-{[2-amino-3-(aminocarbonyl)-9H-pyrido[2,3-b]indol-9-yl]methyl}pyrrolidine-1-carboxylate (xvi-e, 20 mg, 20%). NH4OAc QC conditions. M+1=410.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 4 days
  2. extractionThe mixture was extracted with ethyl acetate (3×30 ml)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by silica gel chromatography (12 g silica, methylene chloride to 90/10 methylene chloride/methanol gradient)

Sources & evidence

ORD record
ord-91c2bb2de6684e999686d44e8e09c9d2
Source dataset
uspto-grants-2012_01
Patent number
US08101604B2

Reaction notes

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