Sodium Hydroxide → tert-butyl 3-(5-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-ylamino)piperidine-1-carboxylate

HRID 1529340Notes

Reaction equation

HRID 1529340 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]2[C:15]([C:28]3[CH:29]=[C:30]([NH:34][CH:35]4[CH2:40][CH2:39][CH2:38][N:37]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:36]4)[CH:31]=[N:32][CH:33]=3)=[CH:16][N:17](S(C3C=CC(C)=CC=3)(=O)=O)[C:12]2=[CH:11][CH:10]=1.[OH-].[Na+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]2[C:15]([C:28]3[CH:29]=[C:30]([NH:34][CH:35]4[CH2:40][CH2:39][CH2:38][N:37]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:36]4)[CH:31]=[N:32][CH:33]=3)=[CH:16][NH:17][C:12]2=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67959766tert-butyl 3-(5-(5-(2,6-difluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-ylamino)piperidine-1-carboxylate

Product 1

HCID 67959652tert-butyl 3-(5-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-ylamino)piperidine-1-carboxylateYield 83.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A solution of tert-butyl 3-(5-(5-(2,6-difluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-ylamino)piperidine-1-carboxylate (33 mg, 0.050 mmol) in THF (1 mL) was treated with NaOH 10N (0.050 mL, 0.500 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: 1-6% MeOH/DCM), affording tert-butyl 3-(5-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-ylamino)piperidine-1-carboxylate (21 mg, 83%). MS (ESI, pos. ion) m/z: 506.3 (M+1) A solution of tert-butyl 3-(5-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-ylamino)piperidine-1-carboxylate (21 mg, 0.042 mmol) in MeOH (1 mL) was treated with HCl, 5-6N in IPA (0.083 mL, 0.415 mmol). The reaction was heated to 50° After 1 h, the reaction was cooled to 23° C., and the product (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 5-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)-N-(piperidin-3-yl)pyridin-3-amine MS (ESI, pos. ion) m/z: 406.2 (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: 1-6% MeOH/DCM)

Sources & evidence

ORD record
ord-641573cc525d4d49af4bfe273362c71d
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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