Chlorosuccinimide → [6-Chloro-3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic Acid Ethyl Ester

HRID 1795290Notes

Reaction equation

HRID 1795290 reaction equation
[CH2:1]([O:3][C:4](=[O:24])[CH2:5][N:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH:12][CH2:13][C:14]([F:22])([F:21])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[C:7]1=[O:23])[CH3:2].[Cl:25]N1C(=O)CCC1=O>ClCCCl>[CH2:1]([O:3][C:4](=[O:24])[CH2:5][N:6]1[C:11]([Cl:25])=[CH:10][N:9]=[C:8]([NH:12][CH2:13][C:14]([F:21])([F:22])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[C:7]1=[O:23])[CH3:2]

Participants

4

Reactant 2

HCID 31398Chlorosuccinimide2×HCID 10290909[3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic acid ethyl ester

Product 1

HCID 11211001[6-Chloro-3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic Acid Ethyl Ester

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A stirred solution of 6.81 g (20.1 mmol) of [3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic acid ethyl ester and 2.42 g (18.1 mmol) of N-chlorosuccinimide in 100 mL of 1,2-dichloroethane was heated to reflux. An additional 242 mg (1.81 mmol) and 75 mg (0.56 mmol) of NCS were added to the reaction mixture after 1 h and 1.5 h, respectively. After 2.5 h total, the solution was cooled to room temperature and partitioned between dichloromethane (150 mL) and sat. aq. NaHCO3 (200 mL). The layers were separated and the aqueous phase was backwashed with dichloromethane (2×200 mL). The combined organic layers were dried over MgSO4 and the solution concentrated to a volume of 10 mL. This liquid was directly loaded onto a SiO2 column and eluted with 65:35 to 55:45 hexane-EtOAc to give the title compound as a yellow solid: 1H NMR (CDCl3) δ 8.68 (d, 1H, 4.8, Hz), 7.83 (ddd,1H, 7.7, 7.7, 1.6 Hz), 7.9 (dd, 1H, 7.9 Hz), 7.40 (dd, 1H, 4.9, 7.3 Hz), 6.96 (s, 1H), 6.49 (br t, 1H, 5.9 Hz), 4.89 (s, 2H), 4.38 (td, 2H, 13.9, 6.5 Hz), 4.26 (q, 2H, 7.1 Hz), 1.30 (t, 3H, 7.1 Hz).

Workup

  1. custompartitioned between dichloromethane (150 mL) and sat. aq. NaHCO3 (200 mL)
  2. customThe layers were separated
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationthe solution concentrated to a volume of 10 mL
  5. washeluted with 65:35 to 55:45 hexane-EtOAc

Sources & evidence

ORD record
ord-8650d90439dd4c3ba37b54fb71c3ec7e
Source dataset
uspto-grants-2006_04
Patent number
US07026324B2

Reaction notes

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