Diisopropylethylamine → 3-[(2-Amino-5-bromo-pyridin-3-ylmethyl)amino]propionic acid ethyl ester

HRID 1362112Notes

Reaction equation

HRID 1362112 reaction equation
Br.[Br:2][C:3]1[CH:4]=[C:5]([CH2:10]Br)[C:6]([NH2:9])=[N:7][CH:8]=1.Cl.[CH2:13]([O:15][C:16](=[O:20])[CH2:17][CH2:18][NH2:19])[CH3:14].C(N(CC)C(C)C)(C)C>CN(C=O)C.C(Cl)Cl.O>[CH2:13]([O:15][C:16](=[O:20])[CH2:17][CH2:18][NH:19][CH2:10][C:5]1[C:6]([NH2:9])=[N:7][CH:8]=[C:3]([Br:2])[CH:4]=1)[CH3:14]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 534200525-Bromo-3-(bromomethyl)pyridin-2-amine hydrobromide

Product 1

HCID 594569683-[(2-Amino-5-bromo-pyridin-3-ylmethyl)amino]propionic acid ethyl esterYield 23.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-bromo-3-bromomethyl-pyridin-2-ylamine hydrobromide (9.41 g, 27.1 mmol) and β-alanine ethyl ester hydrochloride (5.00 g, 32.5 mmol) in DMF (75 mL) was treated with N,N-diisopropylethylamine (16.5 mL, 94.9 mmol). After stirring at room temperature for 4 h, the cloudy mixture was diluted with CH2Cl2 (100 mL) and H2O. The aqueous layer was extracted with CH2Cl2 (2×150 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent removed in vacuo. Purification by column chromatography (silica gel, CH2Cl2/MeOH/Et3N, 95/4.5/0.5 to 80/19.5/0.5) gave the title compound (1.90 g, 23%) as a tan oil: MS (ESI) m/le 302 (M+H)+.

Workup

  1. extractionThe aqueous layer was extracted with CH2Cl2 (2×150 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent removed in vacuo
  6. customPurification by column chromatography (silica gel, CH2Cl2/MeOH/Et3N, 95/4.5/0.5 to 80/19.5/0.5)

Sources & evidence

ORD record
ord-3020d719821f4c968e17bdf981249756
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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