1,2-Dibromoethane → 2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-7-(phenethylthio)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

HRID 1987925Notes

Reaction equation

HRID 1987925 reaction equation
[OH:1][C:2]([CH3:31])([CH3:30])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[NH:15][CH:16]=[C:17]([S:19][CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:18]=2)=[O:13])=[CH:7][C:6]=1[O:28][CH3:29].Br[CH2:33][CH2:34]Br.[OH-].[Na+]>ClC(Cl)C.CCOC(C)=O>[OH:1][C:2]([CH3:31])([CH3:30])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:34][CH2:33][N:15]3[CH:16]=[C:17]([S:19][CH2:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:18]=[C:14]3[C:12]2=[O:13])=[CH:7][C:6]=1[O:28][CH3:29]

Participants

6

Reactant 3

HCID 78391,2-DibromoethaneHCID 14798Sodium HydroxideHCID 67215051N-(4-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(phenethylthio)-1H-pyrrole-2-carboxamide

Product 1

HCID 577250062-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-7-(phenethylthio)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-oneYield 54.8%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of N-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(phenethylthio)-1H-pyrrole-2-carboxamide (20.0 mg, 0.0450 mmol), 1,2-dibromoethane (20.0 μL, 0.227 mmol), NBu4Br (43.5 mg, 0.135 mmol) and 1N NaOH (0.227 mL, 0.227 mmol) in dichloroethane (0.227 mL) was allowed to stir at 50° C. for 4 h. The reaction mixture was cooled to rt, diluted with EtOAc (20 mL), washed with water (×2, 15 mL), brine, dried over anhydrous Na2SO4, concentrated and purified by preparative HPLC: Phenomenex Luna AXIA 5μ C18 21.2×100 mm, 15 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 5 min hold; 20 mL/min, UV detection at 220 nm, 8.949 min retention time to afford 11.5 mg of the title compound as a light yellow solid: 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 6H), 2.86-2.91 (m, 2H), 2.92-2.98 (m, 2H), 3.83 (s, 2H), 3.85 (s, 3H), 4.05-4.11 (m, 2H), 4.24-4.28 (m, 2H), 6.78-6.84 (m, 2H), 6.93 (d, J=8.2 Hz, 1H), 6.96 (d, J=2.2 Hz, 1H), 7.07 (s, 1H), 7.18 (d, J=8.2 Hz, 2H), 7.21 (d, J=7.1 Hz, 1H), 7.26-7.32 (m, 2H); HPLC a) column: Phenomenex Luna 5μ 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/011% H3PO4 to 90% MeOH/10% H2O/0.1% H3PO4; 1 min hold, 4 mL/min UV detection at 220 nm, 3.470 min retention time, (>95%); HPLC b) column: Phenomenex Luna C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold; 4 mL/min, UV detection at 220 nm, 3.461 min retention time; MS (ESI) 467 [M+H]−.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. washwashed with water (×2, 15 mL), brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. custompurified by preparative HPLC
  6. customC18 21.2×100 mm, 15 min gradient, 10% MeOH/90% H2O/0.1% TFA
  7. customto 90% MeOH/10% H2O/0.1% TFA, 5 min

Sources & evidence

ORD record
ord-931c1e178f564926878d0580b8d3d7a0
Source dataset
uspto-grants-2009_06
Patent number
US07553836B2

Reaction notes

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