Hydrochloric Acid → 1-[4-(3-Aminomethyl-phenyl)-piperidin-1-yl]-1-[5-(4-bromo-2-fluoro-benzylamino)-pyridin-3-yl]-methanone trihydrochloride

HRID 489619Notes

Reaction equation

HRID 489619 reaction equation
CC(OC(=O)[N:7]([CH2:44][C:45]1[CH:50]=[CH:49][C:48]([Br:51])=[CH:47][C:46]=1[F:52])[C:8]1[CH:9]=[N:10][CH:11]=[C:12]([C:14]([N:16]2[CH2:21][CH2:20][CH:19]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][N:29](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[CH:23]=3)[CH2:18][CH2:17]2)=[O:15])[CH:13]=1)(C)C.[ClH:54].O1CCOCC1.CCOCC>C(O)(C)C>[ClH:54].[ClH:54].[ClH:54].[NH2:29][CH2:28][C:24]1[CH:23]=[C:22]([CH:19]2[CH2:18][CH2:17][N:16]([C:14]([C:12]3[CH:11]=[N:10][CH:9]=[C:8]([NH:7][CH2:44][C:45]4[CH:50]=[CH:49][C:48]([Br:51])=[CH:47][C:46]=4[F:52])[CH:13]=3)=[O:15])[CH2:21][CH2:20]2)[CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 312751,4-DioxaneHCID 69033035(4-Bromo-2-fluoro-benzyl)-{5-[1-(4-{3-[N,N-bis-(tert-butoxycarbonyl)aminomethyl]-phenyl)-piperidin-1-yl)-methanoyl]-pyridin-3-yl}-carbamic acid dimethyl-ethyl ester

Product 1

HCID 222660311-[4-(3-Aminomethyl-phenyl)-piperidin-1-yl]-1-[5-(4-bromo-2-fluoro-benzylamino)-pyridin-3-yl]-methanone trihydrochloride

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

(4-Bromo-2-fluoro-benzyl)-{5-[1-(4-{3-[N,N-bis-(tert-butoxycarbonyl)aminomethyl]-phenyl}-piperidin-1-yl)-methanoyl]-pyridin-3-yl}-carbamic acid dimethyl-ethyl ester (0.0806 g, 0.1010 mmol) was treated with 4 M HCl in 1,4-dioxane (2.0 mL, 8.0 mmol) and stirred at ambient temperature. After 25 minutes the reaction mixture was diluted with isopropyl alcohol (0.5 mL) and stirring was continued for an additional 2.5 hours. Dripping the reaction solution into ether (40 mL) with vigorous stirring afforded a white precipitate which was collected by filtration, washed with fresh ether (3.0 mL), and dried to afford 1-[4-(3-aminomethyl-phenyl)-piperidin-1-yl]-1-[5-(4-bromo-2-fluoro-benzylamino)-pyridin-3-yl]-methanone trihydrochloride (0.0563 g): 1H NMR (300 MHz, DMSO-d6) δ 8.39 (br s, 2H), 8.16 (d, J=2.7 Hz, 1H), 8.08 (s, 1H), 7.16-7.70 (m, 8H), 4.49-4.64 (br m, 1H), 4.46 (s, 2H), 4.05-4.30 (m, 1H), 4.00 (AB q, J=5.7 Hz, 2H), 3.01-3.25 (m, 1H), 2.77-2.95 (m, 2H), 1.75-1.92 (m, 1H), 1.45-1.75 (br m, 3H); 19F NMR (282 MHz, DMSO-d6) δ-114.1; MS (ESI) m/z 497 (M+H).

Workup

  1. stirringstirring
  2. customafforded a white precipitate which
  3. filtrationwas collected by filtration
  4. washwashed with fresh ether (3.0 mL)
  5. customdried

Sources & evidence

ORD record
ord-55af8ff6c77748dbb6260294f69bcf81
Source dataset
uspto-grants-2005_12
Patent number
US06977263B2

Reaction notes

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