1-Hydroxybenzotriazole → HCID 89835604, compound

HRID 2277084Notes

Reaction equation

HRID 2277084 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]3[C:24](O)=[O:25])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:27]([O:31][C:32](=[O:44])[NH:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:36]=1[CH2:42][NH2:43])([CH3:30])([CH3:29])[CH3:28].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]3[C:24](=[O:25])[NH:43][CH2:42][C:36]3[CH:37]=[C:38]([Cl:41])[CH:39]=[CH:40][C:35]=3[CH2:34][NH:33][C:32]([O:31][C:27]([CH3:30])([CH3:28])[CH3:29])=[O:44])=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 9830421-{[(9H-Fluoren-9-yl)methoxy]carbonyl}piperidine-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11149921Tert-butyl 2-(aminomethyl)-4-chlorobenzylcarbamate

Product 1

HCID 89835604HCID 89835604, compoundYield 76.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of crude (S)-1-[{(9H-Fluoren-9-yl)methoxy}carbonyl]piperidine-2-carboxylic acid (0.75 g, 2.21 mmol), tert-butyl[2-(aminomethyl)-4-chlorobenzyl]carbamate (0.52 g, 1.93 mmol), HOBT (0.26 g, 1.93 mmol), and EDC.HCl (0.48 g, 2.51 mmol) in DMF (5 mL) was stirred under nitrogen at room temperature for 16 h. The reaction mixture was quenched with water (20 mL) and diluted with EtOAc (50 mL). The organic layer was washed sequentially with saturated aqueous NaHCO3 solution (50 mL) and brine solution (50 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by reverse phase combiflash column chromatography (C18; eluent: 10-100% acetonitrile:water) to afford the title compound (0.89 g) as a white solid.

Workup

  1. customThe reaction mixture was quenched with water (20 mL)
  2. additiondiluted with EtOAc (50 mL)
  3. washThe organic layer was washed sequentially with saturated aqueous NaHCO3 solution (50 mL) and brine solution (50 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by reverse phase combiflash column chromatography (C18; eluent: 10-100% acetonitrile:water)

Sources & evidence

ORD record
ord-700c9a2e625c4353b5a785cf5d3996f7
Source dataset
uspto-grants-2015_09
Patent number
US09133147B2

Reaction notes

Loading…