1,2-Dimethoxyethane → 5-{3,6-Diethyl-5-[(1-ethylpropyl)amino]pyrazin-2-yl}-6-methoxyindan-1-one

HRID 1063276Notes

Reaction equation

HRID 1063276 reaction equation
[CH2:1]([C:3]1[C:4]([NH:12][CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])=[N:5][C:6]([CH2:10][CH3:11])=[C:7](I)[N:8]=1)[CH3:2].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CO[CH2:28][CH2:29][O:30][CH3:31].C([O:35][CH2:36][CH3:37])(=O)C>>[CH2:10]([C:6]1[C:7]([C:15]2[CH:14]=[C:13]3[C:37](=[CH:28][C:29]=2[O:30][CH3:31])[C:36](=[O:35])[CH2:17][CH2:16]3)=[N:8][C:3]([CH2:1][CH3:2])=[C:4]([NH:12][CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])[N:5]=1)[CH3:11]

Participants

5

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 222786973,6-diethyl-N-(1-ethylpropyl)-5-iodopyrazin-2-amine

Product 1

HCID 222788255-{3,6-Diethyl-5-[(1-ethylpropyl)amino]pyrazin-2-yl}-6-methoxyindan-1-oneYield 15%

Procedure

A round bottom flask was charged with [PdCl2(dppf)][CH2Cl2] (0.0327 g, 0.044 mmol), potassium acetate (0.4397 g, 4.48 mmol) and bis(pinacolato)diboron (0.416 g, 1.64 mmol) under N2. Anhydrous DMSO (10 mL) and 5-bromo-6-methoxyindan-1-one (0.360 g, 1.49 mmol) were added. After stirring the mixture at 80° C. for 5 hrs, the reaction was cooled to 0° C. The brown solution was partitioned between ethyl acetate and H2O and separated. The organic layer was washed with water (2×5 mL), dried with MgSO4, filtered and concentrated to give 0.367 g of a brown oil. The crude oil was used without further purification. A round bottom flask fitted with a condenser and stir bar was charged with crude intermediate (0.310 mg, 1.10 mmol), 3,6-diethyl-N-(1-ethylpropyl)-5-iodopyrazin-2-amine (0.344 g, 0.90 mmol), [PdCl2(dppf)][CH2Cl2] (0.040 g, 0.055 mmol), potassium phosphate (0.934 g, 4.40 mmol), and anhydrous ethylene glycol dimethyl ether (3 mL) under N2. After stirring at 90° C. for 17 hours the reaction was cooled to ambient temperature, partitioned between ethyl acetate and water and the layers were separated. The organic layer was washed with water (3×10 mL), dried with MgSO4, filtered and concentrated to provide a yellow powder. The crude product was dissolved in a minimum amount of ethyl acetate, and purified via flash chromatography (20% ethyl acetate in heptane) to give 0.050 g (15%) 5-{3,6-diethyl-5-[(1-ethylpropyl)amino]pyrazin-2-yl}-6-methoxyindan-1-one as a yellow powder. 1H NMR (400 MHz, CDCl3) δ 7.42 (s, 1 H), 7.28 (s, 1 H), 4.10-4.20 (m, 2 H), 3.83 (s, 3 H), 3.10-3.20 (m, 2 H), 2.75-2.80 (m, 2 H), 2.69 (br s, 2 H), 2.35-2.60 (s, 2 H), 1.60-1.80 (m, 2 H), 1.50-1.55 (m, 2 H), 1.20-1.40 (m, 6 H), 0.99 (t, J=8 Hz, 6 H). MS (ESI+) for C23H31N3O2 m/z 382.2 (M+H)+. Anal. Calcd. for C23H31N3O2: C, 72.41; H, 8.19; N, 11.01. Found C, 72.20; H, 8.14; N, 10.80.

Workup

  1. customThe crude oil was used without further purification
  2. customA round bottom flask fitted with a condenser
  3. stirringAfter stirring at 90° C. for 17 hours the reaction
  4. custompartitioned between ethyl acetate and water
  5. customthe layers were separated
  6. washThe organic layer was washed with water (3×10 mL)
  7. dry with materialdried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto provide a yellow powder
  11. custompurified via flash chromatography (20% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-b281aea7aea5444292cd77fc305c669a
Source dataset
uspto-grants-2005_11
Patent number
US06964965B2

Reaction notes

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