Triethylamine → tert-Butyl 4-(4-(3-(2-amino-2-methylpropyl)ureido)-3-fluorobenzyl)piperidine-1-carboxylate

HRID 515295Notes

Reaction equation

HRID 515295 reaction equation
[NH2:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)=[CH:4][C:3]=1[F:22].Cl[C:24](OC1C=CC([N+]([O-])=O)=CC=1)=[O:25].[CH3:36][C:37]([NH2:41])([CH3:40])[CH2:38][NH2:39].C(N(CC)CC)C>O1CCCC1>[NH2:41][C:37]([CH3:40])([CH3:36])[CH2:38][NH:39][C:24](=[O:25])[NH:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][CH:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:17])[CH3:18])=[O:14])[CH2:11][CH2:12]2)=[CH:4][C:3]=1[F:22]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 131282-MethylpropylenediamineHCID 821294-Nitrophenyl chloroformateHCID 67193052Tert-butyl 4-(4-amino-3-fluorobenzyl)piperidine-1-carboxylate

Product 1

HCID 86670947tert-Butyl 4-(4-(3-(2-amino-2-methylpropyl)ureido)-3-fluorobenzyl)piperidine-1-carboxylateYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 4-(4-amino-3-fluorobenzyl)piperidine-1-carboxylate (3.44 mmol, 1.06 g) and 4-nitrophenyl chloroformate (3.44 mmol, 0.693 g) were combined in tetrahydrofuran (5 mL) and the reaction stirred at room temperature for 1 hour. 2-Methylpropane-1,2-diamine (3.44 mmol, 0.303 g) and triethylamine (10.31 mmol, 1.043 g) were added and the mixture stirred at room temperature overnight. The mixture was concentrated under reduced pressure and the resulting residue purified by silica gel column chromatography (eluting with dichloromethane to 20% methanol/dichloromethane) to afford the title compound (960 mg). MS (ESI) m/z 423.2 [M+H]+

Workup

  1. stirringthe mixture stirred at room temperature overnight
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe resulting residue purified by silica gel column chromatography (eluting with dichloromethane to 20% methanol/dichloromethane)

Sources & evidence

ORD record
ord-46e7ad5f7586464a8fef1c688ae03645
Source dataset
uspto-grants-2015_08
Patent number
US09108939B2

Reaction notes

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