Hydrochloric Acid → 5-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)-N-(piperidin-3-yl)pyridin-3-amine

HRID 1529341Notes

Reaction equation

HRID 1529341 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:18]3[CH:19]=[C:20]([NH:24][CH:25]4[CH2:30][CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26]4)[CH:21]=[N:22][CH:23]=3)=[CH:16][NH:17][C:12]2=[CH:11][CH:10]=1.Cl.CC(O)C>CO>[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:18]3[CH:19]=[C:20]([NH:24][CH:25]4[CH2:30][CH2:29][CH2:28][NH:27][CH2:26]4)[CH:21]=[N:22][CH:23]=3)=[CH:16][NH:17][C:12]2=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 3776IsopropanolHCID 67959652tert-butyl 3-(5-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-ylamino)piperidine-1-carboxylate

Product 1

HCID 679597735-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)-N-(piperidin-3-yl)pyridin-3-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Conditions

Temperature
23 °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 to 50° After 1 h
  2. customIt was flushed with MeOH (50 mL)
  3. concentrationThe final filtrate was concentrated

Sources & evidence

ORD record
ord-946efe44431a44cabd70e5d4b3aad70d
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

Loading…