Triethylamine → HCID 86592439, compound

HRID 1795299Notes

Reaction equation

HRID 1795299 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH2:5][N:6]1[CH:11]=[CH:10][N:9]=[C:8](Br)[C:7]1=[O:13])[CH3:2].Cl.[N:16]([CH2:19][C@@H:20]([NH2:28])[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[N+:17]=[N-:18].C(OC(N[C@@H](CC1C=CC=CC=1)CO)=O)(C)(C)C.C(N(CC)CC)C>CCO>[CH2:1]([O:3][C:4](=[O:14])[CH2:5][N:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH:28][C@H:20]([CH2:19][N:16]=[N+:17]=[N-:18])[CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:7]1=[O:13])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733675tert-butyl N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]carbamateHCID 11807445(3-Bromo-2-oxo-2H-pyrazin-1-yl)-acetic Acid Ethyl EsterHCID 86592440HCID 86592440, compound

Product 1

HCID 86592439HCID 86592439, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (3-bromo-2-oxo-2H-pyrazin-1-yl)-acetic acid ethyl ester (8.75 g, 33.5 mmol, preparation described in example 17, step J) in EtOH (60 ml) was added (S)-1-azidomethyl-2-phenyl-ethylamine hydrochloride (7.5 g, 35.3 mmol, prepared from (S)-(−)-2-(tertbutoxycarbonylamino)-3-phenyl-1-propanol following the procedure of Horwell et al (J. Med. Chem. 1991, 34, 404–414) and Boc removal under standard HCl(g) conditions) and triethylamine (10.8 ml, 77.6 mmol). The pressure flask was flushed with argon, sealed and the reaction mixture was stirred at 110° C. for 3 days. The reaction mixture was concentrated in vacuo and purified by flash chromatography (silica gel, 20% EtOAc in hexane to 40%) to give (S)-[3-(1-azidomethyl-2-phenylethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic acid ethyl ester as a brown syrup. 1H NMR (CDCl3, 400 MHz): δ 7.36–7.20 (m, 5H); 6.85 (d, J=4.4 Hz, 1H); 6.41 (d, J=4.4 Hz, 1H); 6.20 (bd, J=8 Hz, 1H); 4.58 (A of AB, d, J=17.5 Hz, 1H));); 4.52 (B of AB, d, J=17.5 Hz, 1H)); 4.43–4.33 (m, 1H); 4.25 (q, J=7.3 Hz, 2H); 3.52 (A of ABX, dd, J=12.5, 5 Hz, 1H); 3.40 (B of ABX, dd, J=12.5, 5 Hz, 1H); 3.00 (A of ABX, dd, J=14, 6.7 Hz, 1H); 2.92 (B of ABX, dd, J=14, 7.9 Hz, 1H); 1.29 (t, J=7.3 Hz, 3H).

Workup

  1. customThe pressure flask was flushed with argon
  2. customsealed
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. custompurified by flash chromatography (silica gel, 20% EtOAc in hexane to 40%)

Sources & evidence

ORD record
ord-eccf6c6f67bf40d196d3b16caac68104
Source dataset
uspto-grants-2006_04
Patent number
US07026324B2

Reaction notes

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