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

HRID 2420727Notes

Reaction equation

HRID 2420727 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]([OH:21])([CH3:20])[CH3:19])=[C:12]([O:22][CH3:23])[CH:11]=2)=[O:8])[NH:5][CH:6]=1.Br[CH2:25][CH2:26]Br.[OH-].[Na+]>ClC(Cl)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:7](=[O:8])[N:9]([C:10]3[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]([OH:21])([CH3:19])[CH3:20])=[C:12]([O:22][CH3:23])[CH:11]=3)[CH2:26][CH2:25][N:5]2[CH:6]=1

Participants

6

Reactant 3

HCID 78391,2-DibromoethaneHCID 14798Sodium HydroxideHCID 672152534-Bromo-N-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-1H-pyrrole-2-carboxamide

Product 1

HCID 672154747-Bromo-2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-oneYield 40.1%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 4-bromo-N-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-1H-pyrrole-2-carboxamide (1.50 g, 3.92 mmol), 1,2-dibromoethane (1.68 mL, 19.6 mmol), NBu4Br (1.26 g, 3.93 mmol) and 1N NaOH (19.6 mL, 19.6 mmol) in dichloroethane (19.6 mL) was allowed to stir at 50° C. for 16 h. The reaction mixture was cooled to rt, diluted with EtOAc (150 mL), washed with water, brine, dried over anhydrous Na2SO4 and concentrated. To the resulting brown oil was triturated with EtOAc (25 mL) to give 643 mg of the title compound as a light gray solid: 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 6 H), 2.67 (br. s, 1 H), 3.83 (s, 2 H), 3.85 (s, 3 H), 4.04-4.08 (m, 2 H), 4.22-4.26 (m, 2 H), 6.78 (t, J=5.5 Hz, 2 H), 6.90-6.95 (m, 2 H), 6.99 (s, 1 H); HPLC a) column: PHENOMENEX® Luna 5 μ 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% H3PO4 to 90% MeOH/10% H2O/0.1% H3PO4; 1 min hold, 4 mL/min UV detection at 220 nm, 2.730 min retention time, (99%); 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, 2.748 min retention time; MS (ES) 409 [M+H]+

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. washwashed with water, brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customTo the resulting brown oil was triturated with EtOAc (25 mL)

Sources & evidence

ORD record
ord-34a297b20b8048bb8731fda4143510d0
Source dataset
uspto-grants-2011_06
Patent number
US07956049B2

Reaction notes

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