Sodium Hydroxide → tert-butyl 1-(5-(5-(2-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate

HRID 1529346Notes

Reaction equation

HRID 1529346 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[C:12]2[C:14]([C:27]3[CH:28]=[C:29]([N:33]4[CH2:38][CH2:37][CH:36]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH2:35][CH2:34]4)[CH:30]=[N:31][CH:32]=3)=[CH:15][N:16](S(C3C=CC(C)=CC=3)(=O)=O)[C:11]2=[CH:10][CH:9]=1.[OH-].[Na+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[C:12]2[C:14]([C:27]3[CH:28]=[C:29]([N:33]4[CH2:38][CH2:37][CH:36]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:44])([CH3:43])[CH3:45])[CH2:35][CH2:34]4)[CH:30]=[N:31][CH:32]=3)=[CH:15][NH:16][C:11]2=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67960027tert-butyl 1-(5-(5-(2-fluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate

Product 1

HCID 86709774tert-butyl 1-(5-(5-(2-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamateYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A solution of tert-butyl 1-(5-(5-(2-fluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (125 mg, 0.195 mmol) in THF (3 mL) was treated with NaOH 10N (0.195 mL, 1.948 mmol). The reaction was heated to reflux at 80° C. After 4 h, the solution was cooled to 23° C., concentrated in vacuo and purified by silica gel chromatography (eluent: 1-5% MeOH/DCM), affording tert-butyl 1-(5-(5-(2-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (69 mg, 73%). MS (ESI, pos. ion) m/z: 488.2 (M+1). A solution of tert-butyl 1-(5-(5-(2-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (64 mg, 0.131 mmol) in MeOH (3 mL) and DCM (0.500 mL) was treated with HCl, 36.5-38.0% (0.109 mL, 1.313 mmol). The reaction was heated to 50° C. After 2 h 30 min, the reaction was cooled to 23° C. and concentrated. The residue (as HCl salt) was free-based using a Silicycle Si-propylsulfonic acid ion exchange column (catalog # R51230B). The compound was diluted in MeOH and added to a pad of the resin (wetted and flushed with 10 mL MeOH). It was flushed with MeOH (50 mL), and then the product was “released” using 2.0 M NH3 in MeOH solution (50 ml). The final filtrate was concentrated, affording 1-(5-(5-(2-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-amine. MS (ESI, pos. ion) m/z: 388.3 (M+1).

Workup

  1. temperatureThe reaction was heated
  2. temperaturethe solution was cooled to 23° C.
  3. concentrationconcentrated in vacuo
  4. custompurified by silica gel chromatography (eluent: 1-5% MeOH/DCM)

Sources & evidence

ORD record
ord-79b5a8c1e40445e5b7a911a4b3bedb51
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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